PReD-Bench/PRed-Bench huggingface dataset:
Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer
Authors: Chao-Jun Duan
Yan-Wu Zhou
Chun-Fang Zhang
Rong Li
Yuan-Da Cheng
Yang Gao
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: C14orf166; Clinicopathology; Disease progression; Non-small cell lung cancer; Prognosis.
Affiliations: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China., Department of Gastroenterology, Xiangya Third Hospital, Central South University, Changsha 410013, Hunan Province, China., Institute of Medical Science, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China., Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China .

Abstract:  Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P&lt;0.001) and mRNA levels (P&lt;0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P&lt;0.001), and chemotherapy (P&lt;0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P&lt;0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy. 

Retracted: Yes

PubPeer comments:
 although it was published in 2001, the significant modification in almost all western blot results and attached below. Fig. 1 ![file] Fig. 3 ![file] Fig. 4 ![file] ,
Soil bacterial community as impacted by addition of rice straw and biochar
Authors: Liang Fu
Diankai Gong
Na He
Zuobin Ma
Mingzhu Zhao
Liying Zhang
Hong Gao
Changhua Wang
Wenzhong Zhang
Zhiqiang Tang
Wenjing Zheng
Hui Wang
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: straw; biochar; soil quality; bacterial community; paddy soil
Affiliations: Shenyang Agricultural University, Shenyang, China., Liaoning Rice Research Institute, Shenyang, China., Shenyang Agricultural University, Shenyang, China. .

Abstract:  The application of straw and biochar can effectively improve soil quality, but whether such application impacts paddy soil bacterial community development remains to be clarified. Herein, the impacts of three different field amendment strategies were assessed including control (CK) treatment, rice straw (RS) application (9000 kg ha-1), and biochar (BC) application (3150 kg ha-1). Soil samples were collected at five different stages of rice growth, and the bacterial communities therein were characterized via high-throughput 16S rDNA sequencing. The results of these analyses revealed that soil bacterial communities were dominated by three microbial groups (Chloroflexi, Proteobacteria and Acidobacteria). Compared with the CK samples, Chloroflexi, Actinobacteria, Nitrospirae and Gemmatimonadetes levels were dominated phyla in the RS treatment, and Acidobacteria, Actinobacteria, Nitrospirae and Patescibacteria were dominated phyla in the BC treatment. Compared with the RS samples, Chloroflexi, Acidobacteria, Actinobacteria, and Verrucomicrobia levels were increased, however, Proteobacteria, Gemmatimonadetes, Nitrospirae, and Firmicute levels were decreased in the BC samples. Rhizosphere soil bacterial diversity rose significantly following RS and BC amendment, and principal component analyses confirmed that there were significant differences in soil bacterial community composition among treatment groups when comparing all stages of rice growth other than the ripening stage. Relative to the CK treatment, Gemmatimonadaceae, Sphingomonadaceae, Thiovulaceae, Burkholderiaceae, and Clostridiaceae-1 families were dominant following the RS application, while Thiovulaceae and uncultured-bacterium-o-C0119 were dominant following the BC application. These findings suggest that RS and BC application can improve microbial diversity and richness in paddy rice soil in Northeast China. 

Retracted: No

PubPeer comments:
 Dear authors! A short comment: not  ...were dominated phyla...  but  were dominating phyla  or  dominant phyla. The meaning should be that the phyla were dominating in the microbiome, rather than something dominated the phylum! ,
Transforming growth factor beta1 rescues serum deprivation-induced apoptosis via the mitogen-activated protein kinase (MAPK) pathway in macrophages
Authors: A M Choi
M E Choi
I Petrache
B Y Chin
Journal: Journal of Biological Chemistry (1999)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell death; cell survival; Transforming growth factor beta1 (TGF-beta1); apoptosis; dominant-negative inhibition
Affiliations: Toxicological Sciences, Environmental Health Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.

Abstract:  Cell death and cell survival are central components of normal development and pathologic states. Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine that regulates both cell growth and cell death. To better understand the molecular mechanisms that control cell death or survival, we investigated the role of TGF-beta1 in the apoptotic process by dominant-negative inhibition of both TGF-beta1 and mitogen-activated protein kinase (MAPK) signaling pathways. Murine macrophages (RAW 264.7) undergo apoptosis following serum deprivation, as determined by DNA laddering assay. However, apoptosis is prevented in serum-deprived macrophages by the presence of exogenous TGF-beta1. Using stably transfected RAW 264.7 cells with the kinase-deleted dominant-negative mutant of TbetaR-II (TbetaR-IIM) cDNA, we demonstrate that this protective effect by TGF-beta1 is completely abrogated. To determine the downstream signaling pathways, we examined TGF-beta1 effects on the MAPK pathway. We show that TGF-beta1 induces the extracellular signal-regulated kinase (ERK) activity in a time-dependent manner up to 4 h after stimulation. Furthermore, TGF-beta1 does not rescue serum deprivation-induced apoptosis in RAW 264.7 cells transfected with a dominant-negative mutant MAPK (ERK2) cDNA or in wild type RAW 264.7 cells in the presence of the MAPK kinase (MEK1) inhibitor. Taken together, our data demonstrate for the first time that TGF-beta1 is an inhibitor of apoptosis in cultured macrophages and may serve as a cell survival factor via TbetaR-II-mediated signaling and downstream intracellular MAPK signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 5B. p38 panel. Bands rightmost 2 lanes much more similar than expected. https: imgur.com Ir3jf6t ,
RETRACTED ARTICLE: The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells
Authors: J N Myers
S Kim
M Mandal
A K El-Naggar
M N Younes
S A Jasser
G B Mills
Journal: British Journal of Cancer (2005)
Discipline: CLINICAL MEDICINE
Keywords: PI3K; Akt; thyroid cancer; cell proliferation; apoptosis
Affiliations: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  The phosphatidylinositol 3' kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted. 

Retracted: Yes

PubPeer comments:
 Macrophagic myofasciitis (MMF) is still a problem for neurologists. The vast majority of patients comes from a unique center in France. You have published a limited series of cases in this paper. You wrote: ![file] Since vaccination is a very important information for such a condition, I want to know what is the meaning of  history of vaccination . In the 3 cases in which you have no history, what do you exactly mean? - you have no information about previous vaccination - you know that these subjects have been vaccinated but you don t know what type of vaccines they received - you know that these subjects have been vaccinated but you don t know when they receive vaccines Indeed, the time elapsed during last vaccination and biopsy is very important. According to Gherardi and Authier (see for example their review in Lupus 2012), this time should be at least 18 months. So, if for the 3 cases in which you have no history of vaccination, you cannot establish the correct timing, you should excluded these cases. Such is also the case for the patients in which biopsy as performed less than 18 months after the last vaccination. In your paper, we don t know exactly the total number of such cases but we know that at least one case is included. Since we have no detailed data for all your 16 cases, you should correct the results presenting only the cases fulfilling the correct definition of MMF. Otherwise your data cannot be used for analyzing MMF. ,
USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β‐catenin pathway via Axin1 deubiquitination
Authors: Tielun Tang
Wei Ren
Hai Lin
Liang Yi
Tong Huang
Bing Yan
Qingquan Zhang
Yongjiu Zhang
Journal: Cell biology international (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Axin1; USP44; Wnt/β-catenin; colorectal cancer.
Affiliations: Department of General Surgery, General Hospital of XinJiang Military Command, YouHaoBeiLu, Urumqi, Xinjiang, China., Department of General Surgery, No. 948 Hospital of People's Liberation Army, Changzheng Road, Wusu, Xinjiang, China.

Abstract:  Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/β-catenin pathway. We found that USP44 overexpression increased the Axin1 protein while decreasing β-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/β-catenin pathway. Moreover, we found that two Wnt/β-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/β-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the Axin1 mRNA level. Further study uncovered that USP44 interacted with Axin1 and reduced the ubiquitination of Axin1. Furthermore, Axin1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/β-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy. 

Retracted: No

PubPeer comments:
 In figure 2B, flow cytometric plots for apoptosis of HT29 and HCT116 in oeUSP44 group were the same. ![file] ,
Phorbol ester-induced disruption of the CD4-Lck complex occurs within a detergent-resistant microdomain of the plasma membrane. Involvement of the translocation of activated protein kinase C isoforms
Authors: M Sargiacomo
I Parolini
E Montesoro
A Pace
M Sorice
M P Lisanti
P Ceddia
S Topa
C Peschle
A Pavan
Journal: Journal of Biological Chemistry (1999)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: microdomains; caveolae; signaling; hematopoietic cells; CD4
Affiliations: Department of Hematology-Oncology, Istituto Superiore di Sanità, 00161 Rome, Italy.

Abstract:  Recent studies have highlighted the existence of discrete microdomains at the cell surface that are distinct from caveolae. The function of these microdomains remains unknown. However, recent evidence suggests that they may participate in a subset of transmembrane signaling events. In hematopoietic cells, these low density Triton-insoluble (LDTI) microdomains (also called caveolae-related domains) are dramatically enriched in signaling molecules, such as cell surface receptors (CD4 and CD55), Src family tyrosine kinases (Lyn, Lck, Hck, and Fyn), heterotrimeric G proteins, and gangliosides (GM1 and GM3). Human T lymphocytes have become a well established model system for studying the process of phorbol ester-induced down-regulation of CD4. Here, we present evidence that phorbol 12-myristate 13-acetate (PMA)-induced down-regulation of the cell surface pool of CD4 occurs within the LDTI microdomains of T cells. Localization of CD4 in LDTI microdomains was confirmed by immunoelectron microscopy. PMA-induced disruption of the CD4-Lck complex was rapid (within 5 min), and this disruption occurred within LDTI microdomains. Because PMA is an activator of protein kinase C (PKC), we next evaluated the possible roles of different PKC isoforms in this process. Our results indicate that PMA induced the rapid translocation of cytosolic PKCs to LDTI microdomains. We identified PKCalpha as the major isoform involved in this translocation event. Taken together, our results support the hypothesis that LDTI microdomains represent a functionally important plasma membrane compartment in T cells. 

Retracted: No

PubPeer comments:
null, 
null, 
 #1 Figure 1a. Much more similar than expected. https: imgur.com msmWVqP , 
 Figure 1a. Much more similar than expected. https: imgur.com SSfRwpn , 
 Figure 1a. Much more similar than expected. https: imgur.com JySFfi4 , 
 Figure 1a. Much more similar than expected. https: imgur.com ie1gXru , 
 Figure 1a. Much more similar than expected. https: imgur.com LCCzvDj ,
Magnesium modulates the expression levels of calcification-associated factors to inhibit calcification in a time-dependent manner
Authors: Junxia Zhang
Jingjing Jin
Liwen Cui
Jinsheng Xu
Yaling Bai
Huiran Zhang
Shenglei Zhang
Journal: Experimental and therapeutic medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: core-binding factor α-1; magnesium; matrix Gla protein; osteopontin; time-dependent manner
Affiliations: Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Abstract:  Vascular calcification, a common complication in patients with chronic kidney disease, involves a variety of mechanisms associated with the regulation of calcification-associated factors. Previous clinical studies have indicated that magnesium is involved in the reduction of vascular calcification; however, the mechanism underlying this process remains unknown. The aim of the present study was to investigate the effects of magnesium on β-glycerophosphate (β-GP)-induced calcification and the underlying mechanisms. Primary rat vascular smooth muscle cells (VSMCs) were exposed to 10 mM β-GP in medium with or without the addition of 3 mM magnesium or 2-aminoethoxy-diphenylborate (2-APB; an inhibitor of magnesium transport), for a 14-day period. Calcium deposition and alkaline phosphatase (ALP) activity were measured by Alizarin red staining, quantification of calcium and enzyme-linked immunosorbent assay. The expression levels of core-binding factor α-1 (Cbfα1), matrix Gla protein (MGP) and osteopontin (OPN) were determined by reverse transcription-polymerase chain reaction or western blot analysis, following incubation for 0, 3, 6, 10 and 14 days with the different media. VSMC calcification and ALP activity was reduced significantly in the high-magnesium medium compared with the calcification medium, during the 14-day incubation. The magnesium-induced changes in the VSMCs included a β-GP-induced downregulation of Cbfα1 by day 3 of incubation, an effect that was gradually enhanced over the 14-day period. By contrast, magnesium produced notable increases in MGP and OPN expression levels, with an opposite pattern to that observed in the Cbfα1 expression levels. However, the addition of 2-APB appeared to inhibit the protective effect of magnesium on the VSMCs. Therefore, magnesium was able to effectively reduce β-GP-induced calcification in rat VSMCs by regulating the expression levels of calcification-associated factors in a time-dependent manner. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. About 10% of the papers in this journal (n=169 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 1 appears to show some repetitive elements between or within panels. Boxes of the same color draw attention to areas that look similar. ![file] ,
Enhancement of lipid productivity in oleaginous Colletotrichum fungus through genetic transformation using the yeast CtDGAT2b gene under model-optimized growth condition
Authors: Prabuddha Dey
Nikunj Mall
Monami Chakraborty
Mrinal K Maiti
Atrayee Chattopadhyay
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Oleaginous fungi; lipid production; genetic transformation; Colletotrichum sp. DM06; CtDGAT2b gene
Affiliations: Adv. Lab. for Plant Genetic Engineering, Advanced Technology Development Center, Indian Institute of Technology Kharagpur, Kharagpur, India., Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India., Adv. Lab. for Plant Genetic Engineering, Advanced Technology Development Center, Indian Institute of Technology Kharagpur, Kharagpur, India; Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.

Abstract:  Oleaginous fungi are of special interest among microorganisms for the production of lipid feedstocks as they can be cultured on a variety of substrates, particularly waste lingocellulosic materials, and few fungal strains are reported to accumulate inherently higher neutral lipid than bacteria or microalgae. Previously, we have characterized an endophytic filamentous fungus Colletotrichum sp. DM06 that can produce total lipid ranging from 34% to 49% of its dry cell weight (DCW) upon growing with various carbon sources and nutrient-stress conditions. In the present study, we report on the genetic transformation of this fungal strain with the CtDGAT2b gene, which encodes for a catalytically efficient isozyme of type-2 diacylglycerol acyltransferase (DGAT) from oleaginous yeast Candida troplicalis SY005. Besides the increase in size of lipid bodies, total lipid titer by the transformed Colletotrichum (lipid content ∼73% DCW) was found to be ∼1.7-fold more than the wild type (lipid content ∼38% DCW) due to functional activity of the CtDGAT2b transgene when grown under standard condition of growth without imposition of any nutrient-stress. Analysis of lipid fractionation revealed that the neutral lipid titer in transformants increased up to 1.8-, 1.6- and 1.5-fold compared to the wild type when grown under standard, nitrogen stress and phosphorus stress conditions, respectively. Lipid titer of transformed cells was further increased to 1.7-fold following model-based optimization of culture conditions. Taken together, ∼2.9-fold higher lipid titer was achieved in Colletotrichum fungus due to overexpression of a rate-limiting crucial enzyme of lipid biosynthesis coupled with prediction-based bioprocess optimization. 

Retracted: Yes

PubPeer comments:
 Fig. 4B: More similar than expected. Could authors check this please? ![file] ,
Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply
Authors: Sang-Oh Yoon
John Blenis
Lewis C Cantley
Sang Gyun Kim
Matthew G Vander Heiden
Andrew Y Choo
Sarah J Mahoney
Hieu Vu
Journal: Molecular Cell (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTORC1-signaling pathway; cell growth; anabolic; catabolic processes; energetic stress
Affiliations: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract:  The mTORC1-signaling pathway integrates environmental conditions into distinct signals for cell growth by balancing anabolic and catabolic processes. Accordingly, energetic stress inhibits mTORC1 signaling predominantly through AMPK-dependent activation of TSC1/2. Thus, TSC1/2-/- cells are hypersensitive to glucose deprivation, and this has been linked to increased p53 translation and activation of apoptosis. Herein, we show that mTORC1 inhibition during glucose deprivation prevented not only the execution of death, but also induction of energetic stress. mTORC1 inhibition during glucose deprivation decreased AMPK activation and allowed ATP to remain high, which was both necessary and sufficient for protection. This effect was not due to increased catabolic activities such as autophagy, but rather exclusively due to decreased anabolic processes, reducing energy consumption. Specifically, TSC1/2-/- cells become highly dependent on glutamate dehydrogenase-dependent glutamine metabolism via the TCA cycle for survival. Therefore, mTORC1 inhibition during energetic stress is primarily to balance metabolic demand with supply. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
 Figures 2A and supplemental figure 1E. Much more similar than expected. Legends included. #3 ![file] , 
 Editorial Note to: Glucose Addiction of TSC Null Cells Is Caused by Failed mTORC1-Dependent Balancing of Metabolic Demand with Supply We, the editors of Molecular Cell, were contacted by a concerned reader who informed us about a duplicated image that appears in Figure 2A and Figure S1E of the above paper. These images are pictures of untreated control TSC2- - p53- - mouse embryonic fibroblasts. The authors no longer have access to the original data published 11 years ago, but they believe that these images likely came from the same experiment. Dr. Blenis apologized for the inadvertent duplication and not clearly labeling that these images are from the same experiment. Without access to the original data, a correction is not possible. Given the age of the paper and that the duplication does not compromise the conclusions of the paper, based on the information available to us at this time, we believe that no further action is warranted. https: www.cell.com molecular-cell fulltext S1097-2765(21)00539-6 , 
 #5  The authors no longer have access to the original data published 11 years ago, but they believe that these images likely came from the same experiment. Genotypes different according to the legends. ,
AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion
Authors: Yan-Tao Yin
Wen-Jun Jiang
Xiao-Geng Deng
Rong-Lin Qiu
Jie Zhang
Chi-Hua Wu
Zhi-Xi Li
Journal: Disease Markers (2019)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer; HER2-positive; Adenylate kinase 4; Therapeutic target; Tumor growth
Affiliations: Department of Pediatric Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120 Guangdong Province, China, Department of Pediatric Surgery, Academy of Medical Sciences & Sichuan Provincial People’s Hospital and Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 West Second Section First Ring Road, Chengdu, 610072 Sichuan Province, China, Department of Breast Surgery, Academy of Medical Sciences & Sichuan Provincial People’s Hospital and Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 West Second Section First Ring Road, Chengdu, 610072 Sichuan Province, China

Abstract:  Breast cancer (BC) is a type of malignant tumor originating from the epithelial tissue of the mammary gland, and about 20% of breast cancers are human epidermal growth factor receptor 2 positive (HER2+), which is a subtype with more aggression. Recently, HER2-positive breast cancer is often accompanied by poor prognosis of patients, and targeted therapy showed a promising prospect. To combat this disease, novel therapeutic targets are still needed. Adenylate kinase 4 (AK4) is a member of the adenylate kinase family and is expressed in the mitochondrial matrix. AK4 is involved in multiple cellular functions such as energy metabolism homeostasis. Interestingly, AK4 was observed highly expressed in several tumor tissues, and the involvement of AK4 in cancer development was generally revealed. However, the possible role of AK4 on the growth and development of breast cancer is still unclear. Here, we investigated the possible functions of AK4 on the progression of HER2-positive breast cancer. We found the high expression of AK4 in HER2-positive breast cancer tissues from patients who received surgical treatment. Additionally, AK4 expression levels were obviously correlated with clinical-pathological features, including pTNM stage (P = 0.017) and lymph node metastasis (P = 0.046). We mechanically confirmed that AK4 depletion showed the obvious impairment of cell proliferation and invasion in MCF7 and MDA-MB-231 cells. AK4 also facilitates tumor growth and metastasis of HER2-positive breast cancer in vivo. In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer. 

Retracted: No

PubPeer comments:
 Duplication in Figure 3D: ![file] ,
MicroRNA-411 inhibits malignant biological behaviours of colorectal cancer cells by directly targeting PIK3R3
Authors: Rui Zhang
Jian Zhao
Jian Xu
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; miRNA-411; tumourigenesis; tumour development; expression pattern
Affiliations: Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Insititute, Shenyang, Liaoning 110042, P.R. China.

Abstract:  Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related mortality worldwide. Aberrant expression of miRNAs play important roles in the development and progression of various types of cancers by modulating oncogenic and tumour-suppressor pathways. Therefore, exploring the functions of microRNAs (miRNAs) that specifically contribute to CRC tumourigenesis and tumour development would greatly aid in obtaining more information on CRC and provide new targets for its diagnosis and treatment. miRNA-411 (miR-411) was previously observed to be aberrantly expressed in multiple human cancers. However, the expression pattern, function and underlying molecular mechanism of miR-411 in CRC remain unclear. Therefore, the present study was performed to detect miR-411 expression, investigate the biological roles of miR-411 and identify its mechanism of action in CRC cells. Here, miR-411 expression was significantly downregulated in human CRC tissues and cell lines, and low levels of miR-411 were correlated with lymph node metastasis, distant metastasis and TNM stage. Resumed expression of miR-411 suppressed cell proliferation and invasion but promoted apoptosis in CRC. Additionally, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR-411 in CRC. PIK3R3 was upregulated in the CRC tissues and inversely correlated with miR-411 expression. Downregulation of PIK3R3 had tumour-suppressive effects similar to those of miR-411 overexpression in CRC. Moreover, upregulation of PIK3R3 could rescue the tumour-suppressing effects of miR-411 overexpression in CRC cells. More importantly, miR-411 specifically suppressed the activation of the AKT/mTOR signalling pathway in CRC. Therefore, miR-411 functions as a tumour-suppressive miRNA by directly targeting PIK3R3 and indirectly regulating AKT/mTOR signalling pathway. miR-411 may serve as a new therapeutic target for patients with CRC. 

Retracted: Yes

PubPeer comments:
 The primer sequences seem to be missing from this article. No referral to primers. ![file] Could the authors share the forward and reverse primer sequences, as well as the sequences used for the short hairpin RNAs, in order for the readers to verify specificity and reliability of the presented gene expression data regarding a human non-coding RNA? ![file] ,
Binding of recombinant but not endogenous prion protein to DNA causes DNA internalization and expression in mammalian cells
Authors: Man-Sun Sy
Xingjun Fan
Shaoman Yin
Chaoyang Li
Shuiliang Yu
Journal: Journal of Biological Chemistry (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: recombinant prion protein; DNA binding; KKRPK motif; octapeptide repeat region; pathogenic insertional mutations
Affiliations: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44120, USA.

Abstract:  Recombinant prion protein, rPrP, binds DNA. Both the KKRPK motif and the octapeptide repeat region of rPrP are essential for maximal binding. rPrP with pathogenic insertional mutations binds more DNA than wild-type rPrP. DNA promotes the aggregation of rPrP and protects its N terminus from proteinase K digestion. When rPrP is mixed with an expression plasmid and Ca(2+), the rPrP.DNA complex is taken up by mammalian cells leading to gene expression. In the presence of Ca(2+), rPrP by itself is also taken up by cells in a temperature- and pinocytosis-dependent manner. Cells do not take up rPrP(DeltaKKRPK), which lacks the KKRPK motif. Thus, rPrP is the carrier for DNA and the KKRPK motif is essential for its uptake. When mixed with DNA, a pentapeptide KKRPK, but not KKKKK, is sufficient for DNA internalization and expression. In contrast, whereas the normal cellular prion protein, PrP(C), on the cell surface can also internalize DNA, the imported DNA is not expressed. These findings may have relevance to the normal functions of PrP(C) and the pathogenic mechanisms of human prion disease. 

Retracted: No

PubPeer comments:
 ![file] ,
Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts
Authors: Victor Weitao Lin
Yuk Chun Cheung
Chi Man Tsang
Yibin Feng
Guitao Zhang
Vivian Wai-Yan Lui
Yim Ling Yip
Sai Wah Tsao
Kenneth Chat-Pan Cheung
Journal: BMC Cancer (2013)
Discipline: CLINICAL MEDICINE
Keywords: Cortidis rhizoma; berberine; anti-cancer properties; growth inhibition; invasion
Affiliations: Department of Anatomy, The University of HongKong, HongKong, SAR, China. .

Abstract:  Background: Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. Methods: In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Results: Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Conclusions: Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC. 

Retracted: No

PubPeer comments:
null, 
 image duplication, rotated ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
HER2 as a promising target for cytotoxicity T cells in human melanoma therapy
Authors: Xin Xue
Juan Ma
Deruo Liu
Ge Zhang
Hongxiang Feng
Xiaoran Wu
Wei Li
Huamin Han
Bin Gao
Hua Tao
Changzhen Liu
Yunfeng Zhao
Ge Niu
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Anti-HER2/neu antibody therapy; tumor regression; HER2; human melanoma cells; T cell mediated immunotherapy
Affiliations: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P. R. China.

Abstract:  Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future. 

Retracted: No

PubPeer comments:
 https: retractionwatch.com 2013 10 16 plant-journal-withdraws-paper-or-does-it , 
 But what s the actual issue with this paper...can someone explain it to me? , 
 #2 Nothing is reported wrong with the paper, read the link in #1 ,
Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling
Authors: Joël Beaudouin
Michael R Hübner
Frank Gannon
Heike Brand
Jan Ellenberg
Stefanie Denger
Dominique Manu
George Reid
Raphaël Métivier
Journal: Molecular Cell (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: hERalpha; transcription; estrogen-responsive promoters; ChIP; FRAP
Affiliations: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.

Abstract:  We present an integrated model of hERalpha-mediated transcription where both unliganded and liganded receptors cycle on estrogen-responsive promoters. Using ChIP, FRAP, and biochemical analysis we evaluate hERalpha at several points in these cycles, establishing the ubiquitination status and subnuclear distribution of hERalpha, its mobility, the kinetics of transcriptional activation, and the cyclic recruitment of E3 ligases and the 19S regulatory component of the proteasome. These experiments, together with an evaluation of the inhibition of transcription and proteasome action, demonstrate that proteasome-mediated degradation and hERalpha-mediated transactivation are inherently linked and act to continuously turn over hERalpha on responsive promoters. Cyclic turnover of hERalpha permits continuous responses to changes in the concentration of estradiol. 

Retracted: No

PubPeer comments:
 Possible image duplications![file] ,
Endurance training remodels sperm-borne small RNA expression and methylation at neurological gene hotspots
Authors: Nikolaj Thure Krarup
Mie Mechta
Lars R Ingerslev
Odile Fabre
Ida Donkin
Pattarawan Pattamaprapanont
Brynjulf Mortensen
Romain Barrès
Soetkin Versteyhe
Journal: Clinical Epigenetics (2018)
Discipline: CLINICAL MEDICINE
Keywords: sperm epigenome; lifestyle factors; endurance training; small RNA sequencing; DNA methylation
Affiliations: 1The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., 2Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., 3University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.

Abstract:  Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RRBS), we, respectively, investigated sRNA expression and DNA methylation in pure fractions of motile spermatozoa collected from young healthy individuals before, after 6 weeks of endurance training and after 3 months without exercise. Expression of 8 PIWI interacting RNA were changed by exercise training. RRBS analysis revealed 330 differentially methylated regions (DMRs) after training and 303 DMRs after the detraining period, which were, in both conditions, enriched at close vicinity of transcription start sites. Ontology analysis of genes located at proximity of DMRs returned terms related to neurological function at the trained state and, to a much lesser extent, at the detrained state. Our study reveal that short-term endurance training induces marked remodeling of the sperm epigenome, and identify genes related to the development of the central nervous system as potential hot spots for epigenetic variation upon environmental stress. 

Retracted: No

PubPeer comments:
 One section of thie paper is entitled:  Exercise training remodels methylation of brain genes . But the material of investigation is sperm. DNA methylation is highly developmentally regulated and tissue-specific, how do findings in sperm correlate with the situation in the embryo and, later, in the child and in the adult? ,
<p>Characterization and Anti-Cancerous Effect of <em>Putranjiva roxburghii</em> Seed Extract Mediated Silver Nanoparticles on Human Colon (HCT-116), Pancreatic (PANC-1) and Breast (MDA-MB 231) Cancer Cell Lines: A Comparative Study</p>
Authors: Nayan Mishra
Alpana Joshi
Acharya Balkrishna
Niti Sharma
Vinay Kumar Sharma
Laxmi Bisht
Subrata K Das
Journal: International Journal of Nanomedicine (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Putranjiva; anti-cancer; apoptosis; green synthesis; silver nanoparticles.
Affiliations: Drug Discovery and Development Division, Patanjali Research Foundation Trust, Haridwar, Uttarakhand 249405, India., University of Patanjali, Haridwar, Uttarakhand 249405, India.

Abstract:  Introduction: A comparative study of Putranjiva roxburghii Wall. seed extract and developed silver nanoparticles (PJSNPs) for improving bioavailability that enhance their anti-cancer activity against HCT-116 (colon carcinoma), PANC-1 (pancreatic carcinoma), MDA-MB 231 (breast carcinoma) cell lines was performed. Materials and methods: The green synthesis of PJSNPs (Putranjiva silver nanoparticles) was performed using PJ (Putranjiva) extract, and characterization of synthesized nanoparticles was accomplished through UV-Vis spectrum, X-ray diffraction (XRD), transmission electron microscopy, energy-dispersive X-ray spectroscopy (TEM-EDAX), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and Raman spectroscopy. Results: The results revealed that PJSNPs are homogeneous, spherical in shape, ~8±2 nm in size, and negatively charged with a zeta potential of about -26.71 mV. The cytotoxicity pattern observed was AgNO3 &gt; PJSNPs &gt; PJ extract. The morphological changes of the cells were observed by flow cytometry and also by the DNA ladder pattern on gel electrophoresis, which indicated that the process of cell death occurred via the apoptosis mechanism and PJSNPs were exerting late-stage apoptosis in all the tested cell lines. The small size and negative value of zeta potential could be the factors responsible for greater bioavailability and thus increased uptake by the tumor cells. Conclusion: The MTT assay and morphological changes observed by various methods indicate that the novel PJSNPs are a better anticancer agent than PJ extract. All the above properties make biologically synthesized PJSNPs an important target in the field of anti-cancer drug discovery. 

Retracted: No

PubPeer comments:
 In Figure 2c, a part of a micrograph has been duplicated and presented as something else. ![file] , 
 This article has been corrected. https: doi.org 10.18632 aging.203391 ,
Mapping and characterizing N6-methyladenine in eukaryotic genomes using single-molecule real-time sequencing
Authors: Maya Strahl
Guanzheng Luo
Eric E Schadt
Shijia Zhu
Tao P Wu
Gang Fang
Andrew Chess
Robert Sebra
John Beaulaurier
Andrew Xiao
Ziyang Hao
James A Gregory
Gintaras Deikus
Chuan He
Journal: Genome Research (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: N6-Methyladenine; DNA methylation; SMRT sequencing; Eukaryotic genomes; Mapping
Affiliations: Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Department of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA., Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA., Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, New York 10013, USA.

Abstract:  N6-Methyladenine (m6dA) has been discovered as a novel form of DNA methylation prevalent in eukaryotes; however, methods for high-resolution mapping of m6dA events are still lacking. Single-molecule real-time (SMRT) sequencing has enabled the detection of m6dA events at single-nucleotide resolution in prokaryotic genomes, but its application to detecting m6dA in eukaryotic genomes has not been rigorously examined. Herein, we identified unique characteristics of eukaryotic m6dA methylomes that fundamentally differ from those of prokaryotes. Based on these differences, we describe the first approach for mapping m6dA events using SMRT sequencing specifically designed for the study of eukaryotic genomes and provide appropriate strategies for designing experiments and carrying out sequencing in future studies. We apply the novel approach to study two eukaryotic genomes. For green algae, we construct the first complete genome-wide map of m6dA at single-nucleotide and single-molecule resolution. For human lymphoblastoid cells (hLCLs), it was necessary to integrate SMRT sequencing data with independent sequencing data. The joint analyses suggest putative m6dA events are enriched in the promoters of young full-length LINE-1 elements (L1s), but call for validation by additional methods. These analyses demonstrate a general method for rigorous mapping and characterization of m6dA events in eukaryotic genomes. 

Retracted: No

PubPeer comments:
 Retraction http: www.impactjournals.com oncotarget index.php?journal=oncotarget page=article op=view path[]=18637 Retraction: Data in this paper was plagiarized from u201cClinical application of contrast-enhanced ultrasonography in diagnosis of superficial lymphadenopathy,u201d in the Journal of Ultrasound in Medicine. 2010; 29:735-40. , 
 Note: This article has been retracted. Please see the link below: https: www.oncotarget.com article 18637 ,
OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma
Authors: Jinghan Wang
Mengchao Wu
Zhigang Li
Weidan Ji
Lu Cao
Ying Zhang
Chunguang Li
Xiaoqing Jiang
Changqing Su
Haihua Qian
Shuwen Shen
Yan Yan
Journal: BMC Cancer (2013)
Discipline: CLINICAL MEDICINE
Keywords: OCT4; BIRC5; CCND1; hepatocellular carcinoma; cancer cell survival
Affiliations: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & Institute, Second Military Medical University, 200438, Shanghai, China.

Abstract:  Background: OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. Methods: By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. Results: Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. Conclusion: OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment. 

Retracted: No

PubPeer comments:
 More image overlaps from [this group] . Figure 6c *** ![file] ,