PReD-Bench/PRed-Bench huggingface dataset:
LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2 Axis
Authors: Kun-Peng Zhu
Chun-Lin Zhang
Xiao-Long Ma
Journal: Molecular Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: MMP2; ODRUL; miR-3182; osteosarcoma; progression.
Affiliations: Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China; Institute of Bone Tumor, Tongji University, School of Medicine, Shanghai 200072, P.R. China., Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China; Institute of Bone Tumor, Tongji University, School of Medicine, Shanghai 200072, P.R. China. Electronic address: .

Abstract:  Recent findings have shown that lncRNA dysregulation is involved in many cancers, including osteosarcoma (OS). In a previous study, we reported a novel lncRNA, ODRUL, that could promote doxorubicin resistance in OS. We now report the function and underlying mechanism of ODRUL in regulating OS progression. We show that ODRUL is upregulated in OS tissues and cell lines and correlates with poor prognosis. ODRUL knockdown significantly inhibits OS cell proliferation, migration, invasion, and tumor growth in vitro and in vivo by decreasing matrix metalloproteinase (MMP) expression. A microarray screen combined with online database analysis showed that miR-3182 is upregulated and MMP2 is downregulated in sh-ODRUL-expressing MG63 cells and that miR-3182 harbors potential binding sites for ODRUL and the 3' UTR of MMP2 mRNA. In addition, miR-3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo. A luciferase reporter assay demonstrated that ODRUL could directly interact with miR-3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR-3182 at the posttranscriptional level. Taken together, our study has elucidated the role of oncogenic ODRUL in OS progression and may provide a new target in OS therapy. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] 1) The R value was wrong. For example: Delta E (S1 and T1), NIS = 0.67 eV = 5403.9 cm^-1 (supporting information) Spin Orbit Coupling (SOC), NIS = 0.00333022 eV = 26.86 cm^-1 (supporting information) Based on R = (SOC Delta E)^2 (article) Thus, R = 24.7x10^-6, however R = 25.25x10^6 in manuscript. Maybe, 24.7 ~ 25.25 is rounding error, but 10^-6 and 10^6 are very different. Is is similar difference with the R value of NI-O, MONI-O, MANI-O, NI-S, MONI-S and MANI-S in all state. 2) The K(isc) and R are difference.  The k(ISC) was estimated to be u223c2 and u223c15 times larger for MONI-S and MANI-S, respectively, than for NI-S, whereas the k(ISC) of RNI-O was negligible (Table 1) In table 1, author used R = (SOC Delta E)^2, where as k(ISC) differ to R even though proportional ratio. Thus,  The k(ISC) was estimated to be u223c2 and u223c15 times larger ... is not correct. ,
MMP-2 participates in the sclera of guinea pig with form-deprivation myopia via IGF-1/STAT3 pathway
Authors: Y Sun
Y-X Liu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MMP-2; IGF-1; STAT3; sclera; form-deprivation myopia
Affiliations: Department of Ophthalmology, Affiliated Hospital of Weifang Medical University, Weifang, China. .

Abstract:  Objective: To investigate the expression changes of MMP-2 (matrix metalloproteinases-2) mediated by IGF-1 (insulin-like growth factors-1) STAT3 (signal transducer and activator of transcription 3) pathway in the sclera of the form-deprivation myopia guinea pigs. Materials and methods: Twenty-four three-week-old guinea pigs were randomly divided into 4 groups: group A (Control), B, C and D. Guinea pigs in group A were sacrificed after 21 days without any special treatment. Guinea pigs in group B were sacrificed 7 days after receiving stitch in the right eye. Guinea pigs in group C were sacrificed 14 days after receiving stitch in the right eye. Guinea pigs in group D were sacrificed 21 days after receiving stitch in the right eye. Eyeball refraction and axial length of guinea pigs were measured before sacrifice. Eyeballs of guinea pigs were enucleated after sacrifice. The expressions of IGF-1, STAT3 and MMP-2 in scleral tissue were detected by Western blot. Results: Axial length extension and myopia appeared in the right eye of guinea pigs in group B. The expressions of IGF-1, STAT3 and MMP-2 in the sclera significantly increased after 7 days of occlusion compared with that in control group A (p&lt;0.05). In the right eye of group C, the axial prolongation and myopia formation appeared after 14-day occlusion. The expressions of IGF-1, STAT3 and MMP-2 in sclera significantly increased compared with that in group A (p&lt;0.05). In the right eye of group D, the axial extension and myopia formation occurred. IGF-1, STAT3 and MMP-2 in scleral significantly upregulated 21 days after occlusion (p&lt;0.05). Furthermore, at different stages of deprivation, protein expressions of MMP-2 and IGF-1 in sclera were positively correlated (r = 0.962, p&lt;0.01). Conclusions: Form-deprivation of guinea pigs lead to increased expressions of IGF-1, STAT3 and MMP-2 in the sclera and myopia of guinea pigs. The expressions of IGF-1, STAT3 and MMP-2 increased progressively over the time of deprivation. Additionally, overexpression of MMP-2 mediated by IGF-1/STAT3 pathway in sclera might promote the formation of myopia. 

Retracted: No

PubPeer comments:
 Figure 1. * Blue boxes: Panels B (day 7) and C (day 14) appear to look identical. ![file] ,
Depletion of 14-3-3 zeta elicits endoplasmic reticulum stress and cell death, and increases vulnerability to kainate-induced injury in mouse hippocampal cultures
Authors: Helena P Bonner
Brona M Murphy
Jochen H M Prehn
Manus W Ward
Niamh Murphy
David C Henshall
Journal: Journal of neurochemistry (2008)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 14-3-3 proteins; neurodegenerative diseases; neuronal death; seizures; organotypic hippocampal cultures
Affiliations: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland, UK.

Abstract:  14-3-3 proteins are ubiquitous signalling molecules that regulate development and survival pathways in brain. Altered expression and cellular localization of 14-3-3 proteins has been implicated in neurodegenerative diseases and in neuronal death after acute neurological insults, including seizures. Presently, we examined expression and function of 14-3-3 isoforms in vitro using mouse organotypic hippocampal cultures. Treatment of cultures with the endoplasmic reticulum (ER) stressor tunicamycin caused an increase in levels of 14-3-3 zeta within the ER-containing microsomal fraction, along with up-regulation of Lys-Asp-Glu-Leu-containing proteins and calnexin, and the selective death of dentate granule cells. Depletion of 14-3-3 zeta levels using small interfering RNA induced both ER stress proteins and death of granule cells. Treatment of hippocampal cultures with the excitotoxin kainic acid increased levels of Lys-Asp-Glu-Leu-containing proteins and microsomal 14-3-3 zeta levels and caused cell death within the CA1, CA3 and dentate gyrus of the hippocampus. Kainic acid-induced damage was significantly increased in each hippocampal subfield of cultures treated with small interfering RNA targeting 14-3-3 zeta. The present data indicate a role for 14-3-3 zeta in survival responses following ER stress and possibly protection against seizure injury to the hippocampus. 

Retracted: No

PubPeer comments:
 Perhaps the peer reviewers weren t as skilled at multi-tasking as they believed. *** ![file] , 
 I do not see a funding statement in the text. Could the authors please check? , 
 #1 Only one of the tumors in the second row, and only one in the third row, cast shadows. ,
Effects of lncRNA ANRIL on proliferation and apoptosis of oral squamous cell carcinoma cells by regulating TGF-β/Smad pathway
Authors: Y Mao
S-B Ning
B Guo
M Xiao
S Fu
L Liu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA ANRIL; oral squamous cell carcinoma; proliferation; apoptosis; TGF-β/Smad pathway
Affiliations: Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .

Abstract:  Objective: To investigate the role of the long non-coding ribonucleic acid (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in the proliferation and apoptosis of the oral squamous cell carcinoma (OSCC) cells by regulating the transforming growth factor-beta (TGF-β)/Smad pathway. Patients and methods: Human OSCC cells were cultured, and then transfected with small interfering (si)-ANRIL to inhibit the lncRNA ANRIL and ANRIL-OE to overexpress the lncRNA ANRIL. Next, the flow cytometry was carried out to detect the apoptosis rate, the proliferation was determined via methyl thiazolyl tetrazolium (MTT) assay, and the changes in the protein level were detected through Western blotting (WB). Results: The lncRNA ANRIL was highly expressed in the tissues and serum of patients. The proliferation ability of the cells transfected with si-ANRIL was significantly reduced, while that of the cells transfected with ANRIL-OE was overtly increased. The apoptosis rate was (9.21±5.22)%, (22.3±1.34)%, and (13.21±6.22)% in lncRNA ANRIL-OE group, si-ANRIL group and control group, respectively. The protein expression level of the apoptotic protein active caspase-3 was lowered after the treatment with ANRIL-OE, and the key molecules of the TGF-β/Smad pathway were notably down-regulated after inhibiting ANRIL with si-ANRIL. Conclusions: The lncRNA ANRIL regulates the TGF-β/Smad signaling pathway to promote the proliferation and suppress the apoptosis of OSCC cells. 

Retracted: No

PubPeer comments:
 The authors may want to check their source files. There are multiple image duplications in this manuscript. For example: ![file] and ![file] ,
Sept4/ARTS is required for stem cell apoptosis and tumor suppression
Authors: Andrew J Schile
Sarit Larisch
Samara Brown
Holger Kissel
Shahin Rafii
Travis Gorenc
Hermann Steller
María García-Fernández
Journal: Genes & development (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Inhibitor of Apoptosis Proteins (IAPs); anti-cancer drugs; Sept4 gene; ARTS; tumor development
Affiliations: Laboratory of Apoptosis and Cancer Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.

Abstract:  Inhibitor of Apoptosis Proteins (IAPs) are frequently overexpressed in tumors and have become promising targets for developing anti-cancer drugs. IAPs can be inhibited by natural antagonists, but a physiological requirement of mammalian IAP antagonists remains to be established. Here we show that deletion of the mouse Sept4 gene, which encodes the IAP antagonist ARTS, promotes tumor development. Sept4-null mice have increased numbers of hematopoietic stem and progenitor cells, elevated XIAP protein, increased resistance to cell death, and accelerated tumor development in an Eμ-Myc background. These phenotypes are partially suppressed by inactivation of XIAP. Our results suggest that apoptosis plays an important role as a frontline defense against cancer by restricting the number of normal stem cells. 

Retracted: No

PubPeer comments:
 In Fig. 5G, actin blots from different cells are more similar than one would expect. ![file] ,
A feed-forward regulatory network lncPCAT1/miR-106a-5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells
Authors: Qin Li
Xianghuai Zheng
Jianjiang Zhao
Zhiping Wang
Xiang Sun
Bo Jia
Xiaoling Qiu
Jun Chen
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: feed-forward; miR-106a-5p; osteogenic differentiation; periodontal ligament stem cells; prostate cancer-associated ncRNA transcript-1.
Affiliations: Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, China., Department of Plastic Surgery, Guangzhou School of Clinical Medicine, Southern Medical University (Guangzhou General Hospital of Guangzhou Military Region), Guangzhou, China.

Abstract:  Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self-renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer-associated ncRNA transcript-1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR-106a-5p and then confirmed the direct binding sites of miR-106a-5p on lncPCAT1. Although miR-106a-5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR-106a-5p. Moreover, lncPCAT1 could sponge miR-106a-5p to upregulate miR-106a-5p-targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR-106a-5p, could bind to the promoter of lncPCAT1 and then form a feed-forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA-miRNA feed-forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs. 

Retracted: No

PubPeer comments:
 ![file] Figure 2h: for both H E and Masson staining, it appears that the same slide has been used to image both NC and sh-NC groups. From the materials and methods, it is not clear which are the treatment groups in vivo, to which figure 2h refers to. It is generally stated  4 groups , yet figure 2h shows the pictures from supposedly 5 groups. Can the authors comment on that? ,
Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury
Authors: Hai-Jiang Yao
Quan-Kai Jing
Liang-Yu Song
Su-Hua Shi
Hong-Tao Song
Xiao-Chen Yuan
Wei Lv
Ying-Qiu Mao
Zhi-Gang Li
Yu-Ping Mo
Journal: Neural Plasticity (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: spinal cord injuries; electroacupuncture; neuroprotection; neuronal function recovery; rat models
Affiliations: Department of Rehabilitation, The Third People’s Hospital of Shenzhen, No. 29 Bulan Road, Longgang District, Shenzhen 518112, China, School of Acupuncture, Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Chaoyang District, Beijing 100029, China, Treatment Center of TCM, Beijing Bo’ai Hospital, China Rehabilitation Research Center, School of Rehabilitation Medicine, Capital Medical University, No. 10 Jiaomen North Road, Fengtai District, Beijing 100068, China, Department of Traditional Chinese Medicine, Inner Mongolia People’s Hospital, No. 20 Zhao Wudaroad, Hohhot, Inner Mongolia Autonomous Region 010017, China, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao Street, Dongcheng District, Beijing 100005, China, Research and Experimental Center, Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Chaoyang District, Beijing 100029, China, Department of Rehabilitation, The Third Affiliated Hospital of Beijing University of Chinese Medicine, No. 51 An Wai Xiao Guan Street, Chaoyang District, Beijing 100029, China

Abstract:  In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3. 

Retracted: No

PubPeer comments:
 Figure 1B Much more similar than expected. ![file] ,
NF-κB Down-regulates Expression of the B-lymphoma Marker CD10 through a miR-155/PU.1 Pathway
Authors: Ryan C Thompson
Melanie Herscovitch
Ian Zhao
Thomas D Gilmore
Tyler J Ford
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CD10; NF-κB; miR-155; PU.1; B-cell lymphoma

Abstract:  Cell-surface protein CD10 is a prognostic marker for diffuse large B-cell lymphoma (DLBCL), where high expression of CD10 is found in the germinal center B-cell (GCB) subtype and CD10 expression is low or absent in the activated B-cell (ABC) subtype. As compared with the GCB subtype, patients with ABC DLBCL have a poorer prognosis after standard treatment, and ABC tumor cells have higher NF-κB activity. Herein, we show that increased expression of the NF-κB target micro-RNA miR-155 is correlated with reduced expression of transcription factor PU.1 and CD10 in several B-lymphoma cell lines. Moreover, electromobility shift assays and luciferase reporter assays indicate that PU.1 can directly activate expression from the CD10 promoter. Expression of a DLBCL-derived mutant of the adaptor CARD11 (a constitutive activator of NF-κB) in the GCB-like human BJAB cell line or v-Rel in the chicken DT40 B-lymphoma cell line causes reduced expression of PU.1. The CARD11 mutant also causes a decrease in CD10 levels in BJAB cells. Similarly, overexpression of miR-155, which is known to down-regulate PU.1, leads to reduced expression of CD10 in BJAB cells. Finally, we show that CD10 expression is reduced in BJAB cells after treatment with the NF-κB inducer lipopolysaccharide (LPS). Additionally, miR-155 is induced by LPS treatment or expression of the CARD11 mutant in BJAB cells. These results point to an NF-κB-dependent mechanism for down-regulation of CD10 in B-cell lymphoma: namely, that increased NF-κB activity leads to increased miR-155, which results in decreased PU.1, and consequently reduced CD10 mRNA and protein. 

Retracted: No

PubPeer comments:
 ![file] ,
Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe
Authors: Erikka Carr
Warren D Kruger
Elizabeth Petri Henske
Radka Stoyanova
Marjon van Slegtenhorst
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: TSC1; TSC2; tuberous sclerosis complex; mutations; arginine uptake
Affiliations: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. 

Abstract:  Mutations in either TSC1 or TSC2 cause tuberous sclerosis complex, an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the skin, brain, heart, and kidneys. Homologs for the TSC1 and TSC2 genes have been identified in mouse, rat, Fugu, Drosophila, and in the yeast Schizosaccharomyces pombe. Here we show that S. pombe lacking tsc1+ or tsc2+ have similar phenotypes including decreased arginine uptake, decreased expression of three amino acid permeases, and low intracellular levels of four members of the arginine biosynthesis pathway. Recently, the small GTPase Rheb was identified as a target of the GTPase-activating domain of tuberin in mammalian cells and in Drosophila. We show that the defect in arginine uptake in cells lacking tsc2+ is rescued by the expression of a dominant negative form of rhb1+, the Rheb homolog in S. pombe, but not by expressing wild-type rhb1+. Expression of the tsc2+ gene with a patient-derived mutation within the GAP domain did not rescue the arginine uptake defect in tsc2+ mutant yeast. Taken together, these findings support a model in which arginine uptake is regulated through tsc1+, tsc2+, and rhb1+ in S. pombe and also suggest a role for the Tsc1 and Tsc2 proteins in amino acid biosynthesis and sensing. 

Retracted: No

PubPeer comments:
 Fig 1D: Contrast enhanced. More similar than expected. ![file] ,
DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication
Authors: Ying He
Xi Chen
Deyin Guo
Xi Kang
Jin Zhong
Lin Guo
Hong-Bing Shu
Journal: Virology (2013)
Discipline: MICROBIOLOGY
Keywords: Hepatitis C virus; NS3/4A protease; DDB1; HCV replication; immune evasion
Affiliations: College of Life Sciences, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei 430072, China.

Abstract:  Hepatitis C virus (HCV) infection often causes long-term persistent hepatitis, which eventually leads to liver cirrhosis and hepatocellular carcinoma. HCV-encoded NS3/4A protease plays an important role in HCV immune evasion by cleaving key adapter proteins VISA and TRIF of the RIG-I-like receptors and Toll-like receptors mediated interferon (IFN) induction pathways. To further understand the roles of NS3/4A in HCV life cycle, we identified DDB1 as a cellular substrate of NS3/4A protease by biochemical purification and mass spectrometry analysis. NS3/4A interacted with DDB1 and cleaved DDB1 in HCV-infected cells. Mutagenesis indicated that NS3/4A cleaved DDB1 at the residue of C378. Overexpression of DDB1 potentiated HCV replication, whereas knockdown of DDB1 dramatically inhibited HCV replication. Furthermore, our data indicated that the cleavage of DDB1 by NS3/4A protease was required for HCV replication. Our findings suggest that DDB1 is a cellular substrate of NS3/4A required for HCV replication and provide new insight into the interaction between HCV and host cells. 

Retracted: No

PubPeer comments:
 Some images of immunofluorescent staining reappeared in this manuscript. See figure below. ![file] , 
 Hi, I am Xi Kang, the first author of the paper u201cDDB1 is a cellular substrate of NS34A protease and required for hepatitis C virus replicationu201d. I made unintentional mistakes in presenting the negative control images. We have the original data and will contact the journal for publishing an erratum. The conclusions are unchanged and verified by others. Iu2019m sorry for making this mistake and thank you for your criticism. , 
 Some more deja-vus in the supplement. ![file] , 
 #3 Hi, I m Xi Kang, the first author of this paper. Thank you for pointing out. In the erratum letter we sent back the journal, I ve clarified that u201cFig.4B Fig.5B and Supplementary Fig.8Bu201d I made the unintentional mistake to display the negative control results. We have the original raw data and updated it to the journal for an erratum. The conclusions and results of this article are verified and repeated by others. ,
Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and theTumor Suppressors p16 INK4a andp53
Authors: Joseph N Winnie
Linda A Scott
J Keith Vass
David A F Gillespie
E Kenneth Parkinson
Bradford W Ozanne
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Invasion; v-Fos oncogene; gene expression; fibroblasts; proliferation
Affiliations: Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow G61 1BD, United Kingdom., Beatson
Institute for Cancer Research, Cancer Research UK Beatson
Laboratories, Glasgow G61 1BD, United Kingdom

Abstract:  Invasion is generally perceived to be a late event during the progression of human cancer, but to date there are no consistent reports of alterations specifically associated with malignant conversion. We provide evidence that the v-Fos oncogene induces changes in gene expression that render noninvasive normal human diploid fibroblasts highly invasive, without inducing changes in growth factor requirements or anchorage dependence for proliferation. Furthermore, v-Fos-stimulated invasion is independent of the pRb/p16(INK4a) and p53 tumor suppressor pathways and telomerase. We have performed microarray analysis using Affymetrix GeneChips, and the gene expression profile of v-Fos transformed cells supports its role in the regulation of invasion, independent from proliferation. We also demonstrate that invasion, but not proliferation, is dependent on the activity of the up-regulated epidermal growth factor receptor. Taken together, these results indicate that AP-1-directed invasion could precede deregulated proliferation during tumorigenesis and that sustained activation of AP-1 could be the epigenetic event required for conversion of a benign tumor into a malignant one, thereby explaining why many malignant human tumors present without an obvious premalignant hyperproliferative dysplastic lesion. 

Retracted: No

PubPeer comments:
 This chapter (as well as Chap.28, Appx.F) cites and relies on the flawed conclusions of Janocha et al. [18]. The problem: Janocha et al. [18] is methodologically and technically so seriously flawed that nowhere throughout that study their findings and conclusions can be relied upon. Their  new method simply does not capture the invariance property of functional-differential equations correctly. As a result, symmetries get generated therein which in reality do not exist. For details, please see the full review: https: publons.com publon 31812953 #review-7962984 ,
Psoriasis-associated impairment of CCL27/CCR10-derived regulation leads to IL-17A/IL-22–producing skin T-cell overactivation
Authors: Micha L Davila
Wei-Bei Wang
Yong Wang
James Coyne
Ming Xu
Chao Li
Na Xiong
Journal: Journal of Allergy and Clinical Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: Psoriasis; skin-specific chemokine; CCL27; CCR10; IL-17A
Affiliations: Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center San Antonio, San Antonio, Tex; Department of Veterinary and Biomedical Sciences, Centre for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pa; Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China., Department of Veterinary and Biomedical Sciences, Centre for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pa., Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pa., Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center San Antonio, San Antonio, Tex; Department of Veterinary and Biomedical Sciences, Centre for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pa., Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pa. Electronic address: ., Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center San Antonio, San Antonio, Tex; Department of Veterinary and Biomedical Sciences, Centre for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, Pa. Electronic address: .

Abstract:  Psoriasis-associated suppression of the skin-specific chemokine/receptor CCL27/CCR10 axis leads to enhanced pathogenic IL-17A/IL-22-producing skin T cell activation and inflammation. 

Retracted: No

PubPeer comments:
 Partial image overlap ![file] , 
 Dear Primulina Danxiaensis, Thank you for careful scrutiny of our paper. Indeed, as you pointed out, the representative pictures of the controls of Fig. E5 and E6 are from a same skin section of a Rag1- - recipient mouse transferred with wild-type CD4+ T cells, which is compared to a Rag1- - recipient mouse transferred with CCR10- - CD4+ T cells (in Fig. E5) or a Rag1- -CCR10- - recipient mouse transferred with wild-type CD4+ T cells (in Fig. E6). Please note that CCR10+ - mice are same as wild-type mice except that CCR10+ - mice carry a CCR10-EGFP reporter for purpose of identifying CCR10-expressing cells with the EGFP reporter in the flow cytometric analysis. Na Xiong ,
Phospholipase D mediates nutrient input to mammalian target of rapamycin complex 1 (mTORC1)
Authors: Darin Salloum
Mahesh Saqcena
David A Foster
Limei Xu
Benjamin Perrella
Paige Yellen
Phil S Medlin
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: mTOR; regulation; amino acids; nutrients; Rheb
Affiliations: Department of Biological Sciences, Hunter College of the City University of New York, New York, New York 10065, USA.

Abstract:  The mammalian target of rapamycin (mTOR) is a critical sensor of nutritional sufficiency. Although much is known about the regulation of mTOR in response to growth factors, much less is known about the regulation of mTOR in response to nutrients. Amino acids have no impact on the signals that regulate Rheb, a GTPase required for the activation of mTOR complex 1 (mTORC1). Phospholipase D (PLD) generates a metabolite, phosphatidic acid, that facilitates association between mTOR and the mTORC1 co-factor Raptor. We report here that elevated PLD activity in human cancer cells is dependent on both amino acids and glucose and that amino acid- and glucose-induced increases in mTORC1 activity are dependent on PLD. Amino acid- and glucose-induced PLD and mTORC1 activity were also dependent on the GTPases RalA and ARF6 and the type III phosphatidylinositol-3-kinase hVps34. Thus, a key stimulatory event for mTORC1 activation in response to nutrients is the generation of phosphatidic acid by PLD. 

Retracted: No

PubPeer comments:
 Figure 2A u2013 more similar than expected. Could authors check it please? ![file] ,
The significance of duodenal mucosal atrophy in patients with common variable immunodeficiency: a clinical and histopathologic study
Authors: Gino R Corazza
Ombretta Luinetti
Alessandro Plebani
Vassilios Lougaris
Vincenzo Villanacci
Alessandra Marchese
Alessandra Zilli
Paola I Bianchi
Federico Biagi
Journal: American Journal of Clinical Pathology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Gastrointestinal manifestations; villous atrophy; common variable immunodeficiency; CVID; infectious agents
Affiliations: Coeliac Centre/First Department of Internal Medicine, University of Pavia, Pavia, Italy, Department of Pathology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy, Pediatrics Clinic, University of Brescia, Spedali Civili, Brescia, Italy, Department of Pathology, University of Brescia, Spedali Civili, Brescia, Italy

Abstract:  Gastrointestinal manifestations and villous atrophy can be seen in patients with common variable immunodeficiency (CVID). In some patients, infectious agents may be responsible, whereas in others, celiac disease (CD) may be the cause. In this study, we investigate the causes and the histopathologic features seen in patients with CVID. Eleven patients with CVID and villous atrophy underwent duodenal biopsies, human leukocyte antigen (HLA) typing, and testing for all celiac antibodies. Fifteen patients with CVID and normal villi and 6 patients with CD but without CVID served as controls. Histologic response to a gluten-free diet (GFD) allowed a diagnosis of CD in 3 of 11 patients. In the remaining 8, the lack of a histologic response to a GFD or HLA typing excluded CD. Celiac antibodies gave conflicting results and were of no help. Polymorphonuclear infiltrates and lesions like graft-versus-host disease are seen more often in flat mucosa unresponsive to a GFD. However, the specificity of these findings remains to be determined and response to a GFD remains the only diagnostic criteria for CD in these patients. Villous atrophy was gluten-sensitive in 3 of 11 patients with CVID. It was not related to gluten-responsive CD in most patients. 

Retracted: No

PubPeer comments:
 ![file] In figure 5A, the pictures of different groups (marked in red) were obviously duplicated. , 
 Thank you for your find this issue, I am apologize for my mistakes, i will apply for the PDPDT journal to correct it. Thank you again. ,
METTL3 expression is associated with glycolysis metabolism and sensitivity to glycolytic stress in hepatocellular carcinoma
Authors: Zhixiang Jian
Xiangling Wei
Ye Lin
Xuewen Zhang
Journal: Cancer Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: Hepatocellular carcinoma; METTL3; glycolysis; metaboliosm.
Affiliations: Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China., Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Abstract:  METTL3 is an RNA methyltransferase implicated in the control of cell differentiation and proliferation in embryonic development and cancer. The current study was aimed to explore the function and underlying mechanism of METTL3 in hepatocellular carcinoma (HCC). We evaluated the expression and prognostic significance of METTL3 in 100 HCC cases and TCGA dataset. In HCC cases, both the RNA and protein expression of METTL3 were significantly upregulated and associated with poor prognosis. Gene set enrichment analysis of transcriptional profiles in HCC specimens revealed that METTL3 expression was associated with impaired glucose metabolism and mTOR signal pathway. In Huh-7 and SMMC-7721 HCC cells, downregulation of METTL3 by siRNA interference inhibited glycolytic capacity, which was proved by the decreased intracellular glucose uptake and lactate production. In terms of mechanism, we found mTORC1 activity was impaired by downregulation of METTL3, additional silencing of METTL3 cannot further decrease the phosphorylation level of mTORC1 and glycolysis activity in Rapamycin-treated HCC cells. At last, we observed that downregulation of METTL3 synergizes with the glycolysis inhibitor 2-deoxyglucose (2-DG) to inhibit tumor growth in vitro. Our study provided evidence that METTL3 is involved in the regulation of glycolysis activity in HCC, suggesting that suppression of glycolysis via METTL3 inhibition was a potential treating strategy against HCC. 

Retracted: No

PubPeer comments:
 Generally speaking, 18sRNA or U6 as an internal control used in qRT-PCR is only for the research of miRNA. As for the detection of METTL3, published literature until now does not use 18sRNA as an internal control gene, either. Most literatures use GAPDH or beta actin. Accordingly, the level of METTL3 expression in the authorsu2019 center for the 100 HCC patients would be inaccurate. ![file] , 
 **Figure 5B, I donu2019t think this is an accurate WB band for 4E-BP1** ![file] **As shown in the figure below, the change in 4E-BP1 modular weight of 15 to 20 makes it generally look like this.** ![file] ,
Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to anti-EGFR antibody ior egf/r3 for targeted tumor imaging and therapy
Authors: Anil K Mishra
Ramesh Chandra
Vibha Srivastava
Normando Iznaga-Escobar
Pushpa Mishra
Rakesh Kumar Sharma
Puja Pnwar
Journal: Cancer Biology & Therapy (2005)
Discipline: CLINICAL MEDICINE
Keywords: bifunctional chelating agent; DOTA-Ph-Al; conjugation; monoclonal antibody; anti-EGFR
Affiliations: Division of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.

Abstract:  An appropriate bifunctional chelating agent namely DOTA-Ph-Al was developed for the conjugation with biological vectors (anti EGFr antibody). We hereby report the synthesis of p-bromoacetamidobenzyl derivative of DOTA and its conjugation to monoclonal antibody anti-EGFR ior egf/r3. Immunoconjugate was prepared by conjugation of p-bromoacetamidobenzyl derivative of DOTA with ior egf/r3. Modified antibody was purified by size exclusion chromatography. DOTA-Ph-Al-ior egf/r3 exhibited quantitative 99mTc-labeling (&gt;96%) with specific activity 10-20 mCi/mg of protein and 90Y-labeling with specific activity 2-5 mCi/mg. Immunoreactivity was determined by flow cytometry. Receptor ligand assay on murine cell line EAT and human tumor cell line U-87MG showed Kd = 2.87 nM and 4.86 nM respectively. The stability in serum indicated that 99mTc remained bound to antibodies up to 24h and 98% 90Y was associated with the mAb for five days. Biodistribution characteristics of Ab-conjugate radiolabeled to 99mTc and 90Y radionuclide was examined in BALB/c mice grafted with EAT and athymic mice with U-87MG cell line demonstrated high tumor uptake with 5.5 +/- 1.3 and 7.85 +/- 1.2%ID/g at four and 24 h for 99mTc- DOTA-Ph-AI-ior egf/r3 in EAT tumors after post injection respectively. Maximal radiotracer uptake peaked 17.6 +/- 2.5%ID/g in EAT tumor and 12.89 +/- 0.66% ID/g in U-87MG tumor at 48h for 90Y. The drug excreted through renal routes as the activity in the kidneys was 13.42 +/- 0.33%ID/g at 1 h and 4.51 +/- 1.2%ID/g at 4 h for 99mTc- DOTA-Ph-Al-ior egf/r3. 

Retracted: No

PubPeer comments:
 Table-1 of this paper shows a strange similarity of values with a paper published earlier in the year 2014 (DOI: 10.4161 cbt.3.10.1138)u00b7 ![file] ,
Anti-inflammatory role of Leptin in glial cells through p38 MAPK pathway inhibition
Authors: Aleix Martí
Nohora Martínez
Miren Ettcheto
Ignacio Pedrós
Carme Auladell
Carlos Beas-Zarate
Antoni Camins
Francesc Sureda
Iván Patraca
Miguel Marin
Oriol Busquets
Jaume Folch
Journal: Pharmacological Reports (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Caspase-3; Cytochrome-c; Glial cells; Leptin; iNOS

Abstract:  Background: In the present work, we studied the modulatory effect of Leptin (Lep) against pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFα), interleukin 1-beta (IL1β) and interferon-gamma (IFNγ), in primary glial cell cultures. Methods: Glial cultures were treated with pro-inflammatory cytokines (TNFα, 20ng/ml; IL1β, 20ng/ml; IFNγ 20ng/ml). Cells were pre-treated with Lep 500nM, 1h prior to cytokine treatment. NO released from glial cells was determined using the Griess reaction. Cell viability was determined by the MTT method. Protein expression was determined by western blot. Results: Pre-treatment with 500nM Lep produced an inhibitory effect on inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production after glial cells exposure to pro-inflammatory cytokines. Anti-inflammatory effect can be related to a decrease in P38 MAP Kinase (MAPK) pathway activity. Treatment of glial cell cultures with Lep also reduced the intrinsic apoptotic pathway (cytochrome c release and caspase-3 activation). Conclusions: We suggest that Lep would act as an anti-inflammatory factor in glial cells exposed to pro-inflammatory cytokines, exerting its function on p38 MAPK pathway and reducing NO production. 

Retracted: No

PubPeer comments:
 Two of the smears in Figure 1A appear somewhat similar, after adjusting brightness. Could the authors please provide the original uncropped scans? *** ![file] , 
 A band appears to have been used in both Figure 4B and Figure 6B to represent different conditions. Could the authors please provide the original uncropped scans to address this concern? *** ![file] ,
Type III secretion effectors of the IpaH family are E3 ubiquitin ligases
Authors: Philippe J Sansonetti
Alexandre Chenal
Claude Parsot
John R Rohde
Ashton Breitkreutz
Journal: Cell Host & Microbe (2007)
Discipline: MICROBIOLOGY
Keywords: bacteria; pathogenic; Shigella spp.; type III secretion apparatus; effector proteins
Affiliations: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris, Cédex 15, France.

Abstract:  Many bacteria pathogenic for plants or animals, including Shigella spp., which is responsible for shigellosis in humans, use a type III secretion apparatus to inject effector proteins into host cells. Effectors alter cell signaling and host responses induced upon infection; however, their precise biochemical activities have been elucidated in very few cases. Utilizing Saccharomyces cerevisiae as a surrogate host, we show that the Shigella effector IpaH9.8 interrupts pheromone response signaling by promoting the proteasome-dependent destruction of the MAPKK Ste7. In vitro, IpaH9.8 displayed ubiquitin ligase activity toward ubiquitin and Ste7. Replacement of a Cys residue that is invariant among IpaH homologs of plant and animal pathogens abolished the ubiquitin ligase activity of IpaH9.8. We also present evidence that the IpaH homolog SspH1 from Salmonella enterica can ubiquitinate ubiquitin and PKN1, a previously identified SspH1 interaction partner. This study assigns a function for IpaH family members as E3 ubiquitin ligases. 

Retracted: No

PubPeer comments:
 Fig. 2A u2013 Is it possible that this is an image duplication? Could authors check? ![file] ,
miR‑7‑5p regulates the proliferation and migration of colorectal cancer cells by negatively regulating the expression of Kr�ppel‑like factor 4
Authors: Yangyang Xie
Yidong Xu
Mingjun Dong
Journal: Oncology Letters (2019)
Discipline: CLINICAL MEDICINE
Keywords: Krüppel-like factor 4; colorectal cancer; microRNA-7-5p; migration; proliferation.
Affiliations: Department of Anorectal Surgery, The No. 2 Hospital of Ningbo, Ningbo, Zhejiang 315010, P.R. China.

Abstract:  Previous studies have demonstrated that microRNA-7-5p (miR-7-5p) functions as a tumor suppressor in certain types of human cancer. However, the role of miR-7-5p in colorectal cancer (CRC) remains to be investigated. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the present study demonstrated that miR-7-5p was downregulated in CRC tissues and cell lines. In addition, low miR-7-5p expression is able to predict a poor 5-year overall survival rate for patients with CRC. In vitro studies revealed that miR-7-5p overexpression inhibits cell proliferation and migration. Furthermore, Krüppel-like factor 4 (KLF4), an oncogene in CRC, was validated as a direct target of miR-7-5p. KLF4 expression was negatively correlated with miR-7-5p expression in CRC tissues. Notably, KLF4 overexpression rescued the suppressive effects of miR-7-5p on CRC cell proliferation and migration. In summary, the results of this study demonstrated that miR-7-5p inhibits CRC proliferation and migration by targeting KLF4, which suggests that miR-7-5p is a potential molecular target for the treatment of human CRC. 

Retracted: No

PubPeer comments:
 Figs 3D, 5A. Western Blot analyses. ![file] Could the authors upload complete gels for these images? They bear an unfortunate similarity to some of the products of the  Tadpole Papermill . ,
Peptide YY regulates bone turnover in rodents
Authors: Haruka Okamoto
George D Yancopoulos
Victor Shen
Matthias H Tschöp
Katherine E Wortley
Keith D Anderson
Jim P Herman
Andrew Murphy
Mark W Sleeman
Karen Thabet
David Valenzuela
Karen Garcia
Journal: Gastroenterology (2007)
Discipline: CLINICAL MEDICINE
Keywords: Peptide YY; Pancreatic polypeptide; Neuropeptide Y receptor; Energy balance; Bone mass
Affiliations: Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA.

Abstract:  Background &amp; aims: Peptide YY (PYY) and pancreatic polypeptide (PPY) are members of the neuropeptide Y peptide family. The neuropeptide Y receptor signaling pathway has been implicated in a number of physiologic processes, including the regulation of energy balance and bone mass. To investigate the contribution of endogenous PYY and PPY to these processes, we generated both Pyy- and Ppy-deficient mice. Methods: Pyy(-/-) and Ppy(-/-) mice and their respective wild-type littermates were studied from 8 weeks to 9 months of age. Food intake, metabolic parameters, and locomotor activity were monitored using indirect calorimetry. Body composition and bone parameters were analyzed using dual energy x-ray absorptiometry, histomorphometry, and vertebral compression testing. Results: Studies in these mice showed an osteopenic phenotype specific to the Pyy-deficient line, which included a reduction in trabecular bone mass and a functional deficit in bone strength. Furthermore, female Pyy(-/-) mice showed a greater sensitivity to ovariectomy-induced bone loss compared with wild-type littermates. No food intake or metabolic phenotype was apparent in male or female Pyy(-/-) mice on standard chow. However, female Pyy(-/-) mice on a high-fat diet showed a greater propensity to gain body weight and adiposity. No metabolic or osteopenic phenotype was observed in Ppy-deficient mice. Conclusions: These results indicate that endogenous PYY plays a critical role in regulating bone mass. In comparison, its role in regulating body weight is minor and is confined to situations of high-fat feeding. 

Retracted: No

PubPeer comments:
 Identical food intake in peptide YY (PYY - -) and pancreatic polypeptide (PPY - -) mice ![file] ,
GBP1 exerts inhibitory effects on acute viral myocarditis by inhibiting the inflammatory response of macrophages in mice
Authors: Ya-Nan Zhao
Guang-Jun Xu
Ping Yang
Journal: Biochemistry and Cell Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: GBP1; acute viral myocarditis; apoptose; apoptosis; inflammation
Affiliations: a Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China., b Department of Teaching, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.

Abstract:  Viral myocarditis (VMC) is a condition that could potentially progress to dilated cardiomyopathy or congestive heart failure, making it the leading cause of the untimely death in young adults. Interferon-induced GBP1 encodes much of the GTPase induced by interferon gamma in many eukaryotic cells. However, little is known regarding the effect of GBP1 on acute VMC (AVMC). Hence, this aim of this study was to assess the effect of GBP1 on AVMC. Once the AVMC mouse models were established, the functional role of GBP1 was determined in AVMC. Serum levels of IL-6, TNF-α, and TGF-β, and expression levels of GBP1, MIF, iNOS, and COX-2 were detected, together with the viability and apoptosis of cardiomyocytes. AVMC mice presented with increased levels of TGF-β, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cell apoptosis, but lower expression of GBP1 and viability of cardiomyocytes. Restored GBP1 or depleted macrophages resulted in decreased levels of TGF-β, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cardiomyocyte apoptosis, while increasing cardiomyocyte viability. In conclusion, our results highlight the potential role of GBP1 in inhibiting AVMC development. The experimental results indicate that GBP1 up-regulation and macrophage depletion can alleviate AVMC-related cardial damage by inhibiting inflammatory responses and cardiomyocyte apoptosis while increasing cardiomyocyte viability. 

Retracted: Yes

PubPeer comments:
 I am questioning any clinical relevance of the methodology described in this article. The authors claim that the 5-u00b5m-sized microbubbles enter the cells. How? How will the authors solve the challenge with specificity for their microbubbles (targeted therapy)? I don t see any benefit of using microbubbles if there is no targeting. I you add 5-ALA alone, it will enter all the cells (and accumulate more PP9 in cancer cells). The scanning electron microscopy method used is not described. I am wondering how you get the perfect circular microbubbles presented in Figure 1e? In the in vivo xenograft experiment, you have no description of how you add the ALA, ALA-MB etc. This is important information in light of the discussion regarding specificity. ![file] ,