PReD-Bench/PRed-Bench huggingface dataset:
Long non-coding RNA LOC285194 functions as a tumor suppressor by targeting p53 in non-small cell lung cancer
Authors: Jianxing He
Huaping Zhou
Allen Chen
Jianfei Shen
Min Hou
Qianren Deng
Huan Zou
Xiaoshun Shi
Jin Li
Xiaoxue Zhang
Yingfei Zhang
Kelin She
Jingyi Chen
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: LOC285194; non-small cell lung cancer; tumor-suppressor function; qRT-PCR; clinicopathological features
Affiliations: Southern Medical University, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China., Department of Mathematics, University of California, Berkeley, CA 94720, USA., Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang 317000, P.R. China., Department of the Second Division of Cardiovascular Medicine, Guangdong No. 2 Provincial General Hospital, Guangzhou, Guangdong 510317, P.R. China., Department of Pathology, Affiliated Cancer Hospital andInstitute of Guangzhou Medical University, Guangzhou, Guangdong 510530, P.R. China., State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong 510120, P.R. China., SaiQing Biotech Co. Ltd., Guangzhou, Guangdong 510599, P.R. China.

Abstract:  Recently, LOC285194 has shown a potential tumor-suppressor function in several types of human cancers, but its function in non-small cell lung cancer (NSCLC) remains unknown. This study intended to investigate the biological role of LOC285194 and its clinical significance in NSCLC. LOC285194 was detected by qRT-PCR, and its correlation with clinicopathological features of NSCLC was analyzed. The expression of LOC285194 was knocked down or ectopically expressed in lung cancer cells (A549 and H1299) and tumor cell growth, migration and invasion in vitro were investigated. In addition, the interaction of LOC285194 and target proteins was assessed by RNA pulldown and RNA immunoprecipitation in vitro. The results revealed that the expression of LOC285194 was significantly lower in tumor tissues when compared with the corresponding non-tumor tissues (P&lt;0.001). Its expression was correlated with the tumor size (P=0.027). Kaplan-Meier analysis revealed that patients with lower LOC285194 expression had worse disease-free survival and overall survival rates (P&lt;0.05). RNA protein interaction analysis revealed that p53 was the direct binding target of LOC285194 in NSCLC. Bioinformatics analyses suggested that depletion of LOC285149 could affect its antitumor function through the KRAS/BRAF/SMEK pathway. Our findings indicated that LOC285194 was a novel non-coding prognostic indicator and contributed to tumor suppression by targeting p53 in NSCLC, suggesting that it may be a non-coding target for NSCLC gene therapy. 

Retracted: No

PubPeer comments:
 ![file] ![file] In figure 6b and figure 5b, some images are identical. , 
 #1 More image duplication could be found, **Marked in Blue**: ![file] , 
 #1 Also, a newly found image replication was easily detected, **marked in red box with the red arrow**: ![file] ,
Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma
Authors: Samantha Decandia
Maria Rita Nicotra
Pier Giorgio Natali
Anna Bagnato
Adriana Albini
Francesca Spinella
Laura Rosanò
Valeriana Di Castro
Journal: Molecular Cancer Therapeutics (2006)
Discipline: CLINICAL MEDICINE
Keywords: polyphenol; epigallocatechin-3-gallate; EGCG; green tea; antitumor effect
Affiliations: Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Via delle Messi d'Oro, 156, 00158 Rome, Italy.

Abstract:  The polyphenol epigallocatechin-3-gallate (EGCG), the principal mediator of the green tea, has been known to possess antitumor effect. The endothelin A receptor (ET(A)R)/endothelin-1 (ET-1) axis is overexpressed in ovarian carcinoma representing a novel therapeutic target. In this study, we examined the green tea and EGCG effects on two ovarian carcinoma cell lines, HEY and OVCA 433. EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway. Remarkably, EGCG treatment resulted in a lowering of basal and ET-1-induced angiogenesis and invasiveness mediators, such as vascular endothelial growth factor and tumor proteinase activation. Finally, in HEY ovarian carcinoma xenografts, tumor growth was significantly inhibited by oral administration of green tea. This effect was associated with a reduction in ET-1, ET(A)R, and vascular endothelial growth factor expression, microvessel density, and proliferation index. These results provide a novel insight into the mechanism by which EGCG, affecting multiple ET(A)R-dependent pathways, may inhibit ovarian carcinoma growth, suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which ET(A)R activation by ET-1 plays a critical role in tumor growth and progression. 

Retracted: No

PubPeer comments:
  To the contrary, suicide between midnight and 8 AM is relatively uncommon, but rises abruptly between 8 AM and noon [48 u2013 51].  I might be missing something but this looks silly: the citations are of train suicides; this creates a population bias because those who commit suicide via train would go to the station when it s the least likely they d get caught, and it s most busy in those hours. those who will try to get on a railway away from a stations would still want to do it in daylight to actually see where they re going and where the railway is. also those who commute by train might be more likely to do it there as they come there anyway - usually to work school (and mostly in the mentioned hours) and it only takes a few steps for them. In summary - I m not entirely convinced about this point. ,
MicroRNA‑628‑5p inhibits cell proliferation and induces apoptosis in colorectal cancer through downregulating CCND1 expression levels
Authors: Fei Guo
Jun Xue
Journal: Molecular Medicine Reports (2020)
Discipline: CLINICAL MEDICINE
Keywords: colorectal cancer; microrna-628-5p; proliferation; apoptosis; cyclin d1.
Affiliations: Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075061, P.R. China

Abstract:  MicroRNA (miR)‑628‑5p serves as an antitumor gene in a variety of cancers; however, the role of miR‑628‑5p in colorectal cancer remains largely unclear. The purpose of this study was to investigate the role and mechanism of miR‑628‑5p in colorectal cancer. Reverse transcription‑quantitative PCR (RT‑qPCR), colony formation assays and flow cytometric analysis were used to determine the expression levels of miR‑628‑5p in colorectal cancer tissues and cell lines, and the proliferative ability of colorectal cancer cells. TargetScan version 7.2 and dual‑luciferase reporter assay were performed to predict and confirm miR‑628‑5p target genes. The expression levels of cyclin D1 (CCND1) and related genes were determined using RT‑qPCR or/and western blotting analysis. miR‑628‑5p mimics and CCND1 plasmids were used to overexpress miR‑628‑5p and CCND1; it was demonstrated that the expression levels of miR‑628‑5p were significantly downregulated in colorectal cancer tissues and cell lines. miR‑628‑5p mimic‑transfected cells inhibited the proliferation and induced apoptosis of HT‑29 cells. CCND1, a downstream effector of miR‑628‑5p, promoted the proliferation and suppressed apoptosis of HT‑29 cells, and the effects were reversed by miR‑628‑5p mimics. In conclusion, the present study suggested that colorectal cancer progression may be regulated through the miR‑628‑5p/CCND1 axis, and miR‑628‑5p could be used as a potential diagnostic and prognostic biomarker for colorectal cancer. 

Retracted: No

PubPeer comments:
 ![file] ,
Silencing ARHGAP9 correlates with the risk of breast cancer and inhibits the proliferation, migration, and invasion of breast cancer
Authors: Minwen Ha
Tianyi Wang
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ARHGAP9; breast cancer (BC); cell cycle; invasion; proliferation.
Affiliations: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Abstract:  Breast cancer (BC) is one of the most common malignant tumors in women, and screening relevant genes and markers that are involved in BC tumor genesis and progression is of great value. We previously found that messenger RNA expression of ARHGAP9 was high in BC tissue, but it is unclear whether ARHGAP9 participates in the progression of human BC. In this study, we found that ARHGAP9 expression was correlated with poor patient survival, American Joint Committee on Cancer clinical staging, tumor size, and tumor differentiation. MCF-7 and MDA-MB-231 cells exhibited higher expression of ARHGAP9 than other human BC cell lines (HCC1937, MDA-MB-453, ZR-75-1, and Hs 578T). Knockdown of ARHGAP9 in human BC cells markedly reduced the cell proliferation, migration, and invasive ability of MCF-7 and MDA-MB-231 cells. Furthermore, small interfering RNA (siRNA) of ARHGAP9 also induced G0-G1 cell cycle arrest and apoptosis in MCF-7 and MDA-MB-231 cells. Expressions of cell cycle markers (CDK2 and CCNB1) and invasion-related protein (RhoC and MTA1) were downregulated in siRNA-ARHGAP9-transfected cells. siRNA of ARHGAP9 also inhibited the phosphorylation of mitogen-activated protein kinases in BC cells. In conclusion, the abnormal expression of ARHGAP9 may correlate with the genesis, development, and diagnosis of BC. 

Retracted: Yes

PubPeer comments:
 In Figure 1, the legend and text associated (as well as the whole paper), focuses on ARHGAP9. However the blot and graph in the Figure are labeled as ARHGAP10 when it should be ARHGAP9? ![file] The same for Figure 2A and B, the blots are labeled as ARHGAP10 when it should be ARHGAP9? ![file] ![file] , 
 Fig 3D.  Downregulation of ARHGAP9 induced cell cycle arrest and apoptosis, and inhibited cell invasion and migration in MCFu20107 and MDAu2010MBu2010231 cells. ![file] , 
 Retracted [3 December 2021] -------------------------------------- The above article, published online on 15 June 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked to correct the article. An investigation revealed several flaws and inconsistencies between results presented and experimental methods described, thus the editors consider the conclusions of this article to be invalid. ,
Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats
Authors: Julie A Chowen
Miriam Granado
Laura M Frago
Jesús Argente
Cristina García-Cáceres
María Tuda
Journal: Molecular and Cellular Endocrinology (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: type 1 diabetes; hormonal imbalances; cell death; pituitary; hypothalamus
Affiliations: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

Abstract:  Poorly controlled type1 diabetes is associated with hormonal imbalances and increased cell death in different tissues, including the pituitary, hypothalamus and cerebellum. In the pituitary, lactotrophs are the cell population with the greatest increase in cell death, whereas in the hypothalamus and cerebellum astrocytes are most highly affected. Insulin treatment can delay, but does not prevent, diabetic complications. As ghrelin and growth hormone (GH) secretagogues are reported to prevent apoptosis in different tissues, and to modulate glucose homeostasis, a combined hormonal treatment may be beneficial. Hence, we analyzed the effect of insulin and GH-releasing peptide 6 (GHRP-6) on diabetes-induced apoptosis in the pituitary, hypothalamus and cerebellum of diabetic rats. Adult male Wistar rats were made diabetic by streptozotocin injection (65 mg/kg ip) and divided into four groups from diabetes onset: those receiving a daily sc injection of saline (1 ml/kg/day), GHRP-6 (150 μg/kg/day), insulin (1-8U/day) or insulin plus GHRP-6 for 8 weeks. Control non-diabetic rats received saline (1 ml/kg/day). Diabetes increased cell death in the pituitary, hypothalamus and cerebellum (P&lt;0.05). In the pituitary, insulin treatment prevented diabetes-induced apoptosis (P&lt;0.01), as well as the decline in prolactin and GH mRNA levels (P&lt;0.05). In the hypothalamus, neither insulin nor GHRP-6 decreased diabetes-induced cell death. However, the combined treatment of insulin+GHRP-6 prevented the diabetes induced-decrease in glial fibrillary acidic protein (GFAP) levels (P&lt;0.05). In the cerebellum, although insulin treatment increased GFAP levels (P&lt;0.01), only the combined treatment of insulin+ GHRP-6 decreased diabetes-induced apoptosis (P&lt;0.05). In conclusion, insulin and GHRP-6 exert tissue specific effects in STZ-diabetic rats and act synergistically on some processes. Indeed, insulin treatment does not seem to be effective on preventing some of the diabetes-induced alterations in the central nervous system. 

Retracted: No

PubPeer comments:
 fig 8 a with identical bands ![file] ,
Implication of phospholipase D2 in oxidant-induced phosphoinositide 3-kinase signaling via Pyk2 activation in PC12 cells
Authors: Yoshinori Nozawa
Naoki Matsumoto
Ivan Dikic
Masahiro Koda
Akira Hara
Masashi Ueda
Yoshiko Banno
Kenji Ohguchi
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: phospholipase D; PLD activation; hydrogen peroxide; signal transduction; cellular responses
Affiliations: Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. 

Abstract:  The role of phospholipase D (PLD) activation in hydrogen peroxide (H(2)O(2))-induced signal transduction and cellular responses is not completely understood. Here we present evidence that Ca(2+)-dependent tyrosine kinase, Pyk2, requires PLD activation to mediate survival pathways in rat pheochromocytoma PC12 cells under oxidative stress. The H(2)O(2)-induced phosphorylation of two Pyk2 sites (Tyr(580), and Tyr(881)) was suppressed by 1-butanol, an inhibitor of transphosphatidylation by PLD, and also by transfection of catalytically negative mouse PLD2K758R (PLD2KR). Furthermore, we found that PLD2 was associated with Pyk2 and Src, and that activation of PLD2 was required for H(2)O(2)-enhanced association of Src with Pyk2 leading to full activation of Pyk2. H(2)O(2)-induced phosphorylation of Akt and p70S6K was dependent on phosphatidylinositol 3-kinase (PI3K) activity and was abolished by 1-butanol but not t-butanol. Furthermore, the PI3K/Akt activation in response to H(2)O(2) was reduced by transfection of either PLD2KR or the dominant negative Pyk2DN. This study is the first demonstration that PLD2 activation is implicated in Src-dependent phosphorylation of Pyk2 (Tyr(580) and Tyr(881)) by promoting the complex formation between Pyk2 and activated Src in PC12 cells exposed to H(2)O(2), thereby resulting in activation of the survival signaling pathway PI3K/Akt/p70S6K. 

Retracted: No

PubPeer comments:
 Figure 1: More similar than expected. Could authors check this please? ![file] ,
LncRNA SNHG1 promotes cell proliferation in laryngeal cancer via Notch1 signaling pathway
Authors: Y-C Xu
J-J Zuo
Z-Z Tao
T Liu
F Li
A-Y Zheng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; SNHG1; laryngeal cancer; progression; Notch1 pathway
Affiliations: Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. .

Abstract:  Objective: We aimed at elucidating the potential function of long noncoding ribonucleic acids (lncRNAs) small nucleolar RNA host gene 1 (SNHG1) in the progression of laryngeal cancer (LC) and its underlying mechanism. Patients and methods: Relative level of SNHG1 in LC tissues and controls was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Its expression in LC patients with different tumor stages and statues of lymph node metastasis was examined as well. Correlation between SNHG1 expression and prognosis of LC patients was evaluated by the Kaplan-Meier method. SNHG1 siRNA (si-SNHG1) was constructed for downregulation of SNHG1 expression. Potential effects of downregulated SNHG1 on viability and proliferation of LC cells were detected by cell counting kit-8 (CCK-8) and colony formation assay, respectively. After knockdown of SNHG1, relative levels of Notch1 and hairy, and enhancer of split homolog-1 (Hes1) were determined by qRT-PCR and Western blot. Regulatory effects of SNHG1/Notch1 axis on biological behaviors of LC were finally evaluated. Results: SNHG1 was upregulated in LC tissues than that of controls. Besides, its level was higher in LC with T3-T4 relative to those of T1-T2. Higher abundance of SNHG1 was identified in LC patients with lymph node metastasis compared with those non-metastatic patients. Survival analysis indicated that LC patients with high-level SNHG1 had worse overall survival. Knockdown of SNHG1 in Tu212 and Hep2 cells downregulated relative levels of Notch1 and Hes1. Moreover, SNHG1 knockdown resulted in decreased viability and proliferative ability of LC cells. Notch1 overexpression could reverse the regulatory effects of SNHG1 on viability and proliferation of LC cells. Conclusions: LncRNA SNHG1 is highly expressed in LC tissues. It promotes the proliferation of LC cells by inhibiting Notch1 pathway, thereby promoting the progression of LC. 

Retracted: No

PubPeer comments:
 The operator defined in Definition 6 is not order-preserving with respect to the order relation defined in Definition 4. This means that Theorem 4 does not hold although the authors claimed that it can be easily proved. The operator defined in Definition 7 is even not well defined because the involved so-called PFNs may not be well ranked according to the order relation defined in Definition 4. The methods for multiple attribute decision making based on such notions are meaningless. See also https: pubpeer.com publications 3B9236D4BDD6177F4D5085195AC445 ![file] ![file] ![file] ![file] , 
 A part of the reference list is attached. The reference list contains 77 papers in total of which 30 are authored by G.W. Wei and his co-authors. ![file] ![file] ![file] ,
Yeast Chfr homologs retard cell cycle at G1 and G2/M via Ubc4 and Ubc13/Mms2-dependent ubiquitination
Authors: Charles Brenner
Scott A Gerber
Kathryn C Christensen
Greta L Loring
Journal: Cell Cycle (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Chfr; ubiquitin ligase; cell cycle; Ubc4; Ubc13/Mms2
Affiliations: Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.

Abstract:  Checkpoint with forkhead-associated and RING (Chfr) is a ubiquitin ligase (E3) that establishes an antephase or prometaphase checkpoint in response to mitotic stress. Though ubiquitination is essential for checkpoint function, the sites, linkages and ubiquitin conjugating enzyme (E2) specificity are controversial. Here we dissect the function of the two Chfr homologs in S. cerevisiae, Chf1 and Chf2, overexpression of which retard cell cycle at both G(1) and G(2). Using a genetic assay, we establish that Ubc4 is required for Chf2-dependent G(1) cell cycle delay and Chf protein turnover. In contrast, Ubc13/Mms2 is required for G(2) delay and does not contribute to Chf protein turnover. By reconstituting cis and trans-ubiquitination activities of Chf proteins in purified systems and characterizing sites modified and linkages formed by tandem mass spectrometry, we discovered that Ubc13/Mms2- dependent modifications are a distinct subset of those catalyzed by Ubc4. Mutagenesis of Lys residues identified in vitro indicates that site-specific Ubc4-dependent Chf protein autoubiquitination is responsible for Chf protein turnover. Thus, combined genetic and biochemical analyses indicate that Chf proteins have dual E2 specificity accounting for different functions in the cell cycle. 

Retracted: No

PubPeer comments:
 Figure 2B,3A,3C showed unexpected similar plots. Could the authors please explain? ![file] ![file] ![file] ,
PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling
Authors: Peihao Zheng
Honggang Guo
Yi Liu
Siqi Han
Guangchao Li
Fei Luo
Journal: Biochemical and Biophysical Research Communications (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Multiple myeloma; NF-κB pathway; PSMB4; Proteasome; miR-21.
Affiliations: Department of Hematology, Navy General Hospital, Beijing 100048, China., School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China., Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China., Department of Stomatology, Jinling Hospital, Nanjing 210002, China., Department of Hematology, Navy General Hospital, Beijing 100048, China. Electronic address: .

Abstract:  Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have a flipped image ![file] ,
Ameliorated hepatic insulin resistance is associated with normalization of microsomal triglyceride transfer protein expression and reduction in very low density lipoprotein assembly and secretion in the fructose-fed hamster
Authors: Stephen C Van Iderstine
Linda Szeto
Andre Carpentier
Kristine D Uffelman
Robin Buckingham
Nathalie Leung
Gary F Lewis
Khosrow Adeli
Changiz Taghibiglou
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: insulin resistance; fructose-induced; VLDL oversecretion; rosiglitazone; glucose production rate
Affiliations: Department of Medicine, Division of Endocrinology and Metabolism, University Health Network, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 2C4, Canada.

Abstract:  To determine whether reduction of insulin resistance could ameliorate fructose-induced very low density lipoprotein (VLDL) oversecretion and to explore the mechanism of this effect, fructose-fed hamsters received placebo or rosiglitazone for 3 weeks. Rosiglitazone treatment led to normalization of the blunted insulin-mediated suppression of the glucose production rate and to a approximately 2-fold increase in whole body insulin-mediated glucose disappearance rate (p &lt; 0.001). Rosiglitazone ameliorated the defect in hepatocyte insulin-stimulated tyrosine phosphorylation of the insulin receptor, IRS-1, and IRS-2 and the reduced protein mass of IRS-1 and IRS-2 induced by fructose feeding. Protein-tyrosine phosphatase 1B levels were increased with fructose feeding and were markedly reduced by rosiglitazone. Rosiglitazone treatment led to a approximately 50% reduction of VLDL secretion rates (p &lt; 0.05) in vivo and ex vivo. VLDL clearance assessed directly in vivo was not significantly different in the FR (fructose-fed + rosiglitazone-treated) versus F (fructose-fed + placebo-treated) hamsters, although there was a trend toward a lower clearance with rosiglitazone. Enhanced stability of nascent apolipoprotein B (apoB) in fructose-fed hepatocytes was evident, and rosiglitazone treatment resulted in a significant reduction in apoB stability. The increase in intracellular mass of microsomal triglyceride transfer protein seen with fructose feeding was reduced by treatment with rosiglitazone. In conclusion, improvement of hepatic insulin signaling with rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, is associated with reduced hepatic VLDL assembly and secretion due to reduced intracellular apoB stability. 

Retracted: No

PubPeer comments:
 There are undeclared splicing traces in the immunoblot results of FIG 2B and 2C. ![file] ,
LW-214, a newly synthesized flavonoid, induces intrinsic apoptosis pathway by down-regulating Trx-1 in MCF-7 human breast cells
Authors: Jing Yao
Di Pan
Li Zhao
Zhiyu Li
Wei Li
Hanchi Miao
Libin Wei
Qinglong Guo
Journal: Biochemical Pharmacology (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ASK1; Apoptosis; Chrysin (PubChem CID: 5281607); DAPI (PubChem CID: 2954); DMSO (PubChem CID: 679)
Affiliations: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China., School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China., State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: .

Abstract:  In this study, the anticancer effect of LW-214, a newly synthesized flavonoid, against MCF-7 human breast cancer cells and the underlying mechanisms were investigated. LW-214 triggered the mitochondrial apoptotic pathway by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm) and caspase-9 activation, degradation of poly (ADP-ribose) polymerase (PARP), cytochrome c (Cyt c) release and apoptosis-inducing factor (AIF) transposition. Further research revealed that both the reactive oxygen species (ROS) generation and the apoptosis signal regulating kinase 1 (ASK1) activation by LW-214 were induced by down-regulating the thioredoxin-1 (Trx-1) expression. The ROS elevation and ASK1 activation induced a sustained phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125, as known as JNK inhibitor, almost reversed LW-214-induced apoptosis in MCF-7 cells. Overexpression of Trx-1 in MCF-7 cells attenuated LW-214-mediated apoptosis as well as the JNK activation and reversed the expression of mitochondrial apoptosis-related protein. Accordingly, the in vivo study showed that LW-214 exhibited a potential antitumor effect in BALB/c species mice inoculated MCF-7 tumor with low systemic toxicity, and the mechanism was the same as in vitro study. Taken together, these findings indicated that LW-214 may down-regulated Trx-1 function, causing intracellular ROS generation and releasing the ASK1, and lead to JNK activation, which consequently induced the mitochondrial apoptosis in vitro and in vivo. 

Retracted: No

PubPeer comments:
 In Figure 6F, two flow cytometry dot plots share surprisingly many data points (LW-214 vs Trx-1 OE + LW-214). This is true only for the Q2 gating. ![file] ,
Signal transducer and activator of transcription 3 inhibition enhances vemurafenib sensitivity in colon cancers harboring the BRAF V600E mutation
Authors: Na Song
Xiaofang Che
Yanrong Li
Kezuo Hou
Yang Zhou
Yunpeng Liu
Qiwei Wang
Meihui Cao
Ming Bai
Ling Xu
Yuanhe Wang
Jingdong Zhang
Kai Wang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; colon cancer; proliferation; signal transducer and activator of transcription 3; vemurafenib.
Affiliations: Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China., Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China., Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.

Abstract:  The BRAFV600E inhibitor vemurafenib is widely used to treat melanomas harboring the activated BRAFV600E mutation; however, vemurafenib showed poor efficacy in colon cancer, which impeded its clinical application for colon cancer patients with this mutation. The specific mechanism of vemurafenib resistance is not clear in colon cancer. In this study, we demonstrated that signal transducer and activator of transcription 3 (STAT3) activation influenced vemurafenib sensitivity in BRAFV600E mutant colon cancer cells. When vemurafenib was applied to two colon cancer cell lines with the BRAFV600E mutation, STAT3 was continuously activated after 6 hours. Furthermore, BCL-2 was upregulated in RKO colon cancer cells, while STAT3 remained unchanged in HT-29 colon cancer cells. This suggested that STAT3 signaling might be involved in vemurafenib sensitivity. Combining the STAT3 inhibitor STATTIC with vemurafenib further inhibited cell proliferation and promoted apoptosis by downregulating STAT3 and BCL-2 expression in RKO cells. Further studies showed that interleukin 6 (IL-6) secretion increased after RKO cells were treated with vemurafenib. STAT3 activation was induced by adding IL-6 to the supernatant, and IL-6 increased STAT3 and BCL-2 expression and antagonized vemurafenib sensitivity in HT-29 cells. Together, these results suggest that STAT3 activation maybe related to vemurafenib sensitivity in colon cancer cells, and that combining STAT3 inhibitors with vemurafenib may be a promising treatment for BRAFV600E mutant colon cancers. 

Retracted: No

PubPeer comments:
 In FIGURE 1B, we can see seemingly the same cluster in the third and fourth image of flow cytometry. In FIGURE 1C, the two strips of PUMA and cleaved-PARP in the HT-29 group are the same. In FIGURE 3C, there are three altered strips of p-STAT3 (vemurafenib-IL6 AB-, vemurafenib-IL6 AB+ and vemurafenib+IL6 AB+). In FIGURE 5A, one of the strips of PUMA (vemurafenib- stattic+) was alter deliberately (possibly by Photoshop). (see attached files)![file] ![file] ![file] ,
Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade
Authors: Hiroshi Shibuya
Takashi Kadowaki
Yasuhiro Takeuchi
Ichiro Takada
Yukiko Gotoh
Toshimasa Yamauchi
Kunihiro Matsumoto
Satoko Ogawa
Junn Yanagisawa
Miyuki Suzawa
Fumiaki Ohtake
Shigeaki Kato
Journal: Nature Cell Biology (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Pluripotent mesenchymal stem cells; adipogenesis; osteoblasts; cytokines; interleukin-1
Affiliations: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

Abstract:  Pluripotent mesenchymal stem cells in bone marrow differentiate into adipocytes, osteoblasts and other cells. Balanced cytodifferentiation of stem cells is essential for the formation and maintenance of bone marrow; however, the mechanisms that control this balance remain largely unknown. Whereas cytokines such as interleukin-1 (IL-1) and tumour-necrosis factor-alpha (TNF-alpha) inhibit adipogenesis, the ligand-induced transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), is a key inducer of adipogenesis. Therefore, regulatory coupling between cytokine- and PPAR-gamma-mediated signals might occur during adipogenesis. Here we show that the ligand-induced transactivation function of PPAR-gamma is suppressed by IL-1 and TNF-alpha, and that this suppression is mediated through NF-kappaB activated by the TAK1/TAB1/NF-kappaB-inducing kinase (NIK) cascade, a downstream cascade associated with IL-1 and TNF-alpha signalling. Unlike suppression of the PPAR-gamma transactivation function by mitogen-activated protein kinase-induced growth factor signalling through phosphorylation of the A/B domain, NF-kappaB blocks PPAR-gamma binding to DNA by forming a complex with PPAR-gamma and its AF-1-specific co-activator PGC-2. Our results suggest that expression of IL-1 and TNF-alpha in bone marrow may alter the fate of pluripotent mesenchymal stem cells, directing cellular differentiation towards osteoblasts rather than adipocytes by suppressing PPAR-gamma function through NF-kappaB activated by the TAK1/TAB1/NIK cascade. 

Retracted: Yes

PubPeer comments:
 A Retraction to this article was published on 31 October 2014 https: www.nature.com articles ncb3068 ,
The PVT1/miR-216b/Beclin-1 regulates cisplatin sensitivity of NSCLC cells via modulating autophagy and apoptosis
Authors: Xiaobing Han
Liangxin Chen
Liangfeng Chen
Zhongzhou Hu
Journal: Cancer Chemotherapy and Pharmacology (2019)
Discipline: CLINICAL MEDICINE
Keywords: Autophagy; Beclin-1; Cisplatin sensitivity; NSCLC; PVT1
Affiliations: Department of Oncology, Xinyang Central Hospital, No. 1 Siyi Road, Shihe District, Xinyang, 464000, China. ., Department of Oncology, Xinyang Central Hospital, No. 1 Siyi Road, Shihe District, Xinyang, 464000, China.

Abstract:  Purpose: The efficacy of cisplatin-based chemotherapy remains an open question for chemo-resistance in non-small cell lung cancer (NSCLC). This study aimed to explore the role and mechanism of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) in cisplatin sensitivity of NSCLC. Methods: Paired tumor and adjacent tissues were collected from forty patients with NSCLC. The clinical value of PVT1 was investigated according to clinicopathological parameters of patients. Cisplatin-sensitive or -resistant cells (A549 or A549/DDP) were used for in vitro experiments. Cell viability, apoptosis, autophagy and animal experiments were conducted to investigate cisplatin sensitivity. The expressions of PVT1, microRNA-216b (miR-216b) and apoptosis- or autophagy-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot assay, respectively. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to probe the interaction between miR-216b and PVT1 or Beclin-1. Results: PVT1 was highly expressed and associated with poor prognosis of NSCLC patients (*P &lt; 0.05). PVT1 knockdown enhanced cisplatin-induced viability inhibition and apoptosis induction in A549/DDP cells, but addition of PVT1 caused an opposite effect in A549 cells (*P &lt; 0.05, #P &lt; 0.05). Moreover, accumulation of PVT1 facilitated autophagy of NSCLC cells and tumor growth in vivo (*P &lt; 0.05, #P &lt; 0.05). In addition, miR-216b interacted with PVT1 or Beclin-1. Beclin-1 reversed miR-216b-mediated effect on autophagy and apoptosis of NSCLC cells (*P &lt; 0.05,#P &lt; 0.05). Besides, Beclin-1 protein expression was regulated by PVT1 and miR-216b (*P &lt; 0.05, #P &lt; 0.05). Conclusions: PVT1 may function as a competing endogenous RNA for miR-216b to inhibit cisplatin sensitivity of NSCLC through regulating apoptosis and autophagy via miR-216b/Beclin-1 pathway, providing a novel target for improving chemo-therapy efficacy of NSCLC. 

Retracted: No

PubPeer comments:
 Fig 2c.  Knockdown of PVT1 inhibits cisplatin resistance of A549 DDP cells by modulating apoptosis and autophagy. ... c Cell apoptosis was detected in A549 DDP cells with shPVT1 transfection and cisplatin treatment by flow cytometry. I am admiring the regularity of the stippling in these flow-cytometry scatterplots. ![file] ,
Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1
Authors: Pascal Schneider
Rodrigo Herrera-Molina
Lisette Leyton
María de la Luz Aylwin
Constanze I Seidenbecher
Horacio Maldonado
Andrew F G Quest
Renato Frischknecht
Claudio Hetz
Eckart D Gundelfinger
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: Thy-1; α(V)β(3) integrin; neurite outgrowth; axonal retraction; astrocyte-neuron communication
Affiliations: Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Abstract:  Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)β(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)β(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)β(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)β(3) integrin restricted neurite outgrowth. Likewise, α(V)β(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)β(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)β(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)β(3) integrin. Binding of α(V)β(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)β(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage. 

Retracted: No

PubPeer comments:
 Figure 2C. * Red boxes. In the Thy-1 panel, lanes 3 and 4 look more similar to each other than expected. ![file] ,
Long non-coding RNA DLEU2 promotes the progression of esophageal cancer through miR-30e-5p/E2F7 axis
Authors: Rui Wang
Youbin Cui
Tianyu Lu
Hongfei Cai
Journal: Biomedicine & Pharmacotherapy (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: E2F7; Esophageal cancer; lncRNA DLEU2; miR-30e-5p.
Affiliations: Department of Thoracic Surgery, the First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: .

Abstract:  Background: Emerging evidences have proven the important roles of lncRNAs in tumorigenesis and cancer biology. However, the function of lncRNA DLEU2 in the progression of esophageal cancer (EC) has not been elaborated. In the present study, we aimed to investigate the effects of lncRNA DLEU2 on the progression of EC and the underlying mechanism. Methods: In this study, lncRNA DLEU2 was silenced by siRNA interference in EC cell lines Eca-109 and KYSE-150, and its expression was up-regulated in TE-1 cells by transfection with pcDNA3.1-DLEU2, and its biological functions were examined. Then, bioinformatics analysis and dual-luciferase reporter assay were used to identify the binding miRNA of lncRNA DLEU2 and the target gene of miRNA. In addition, loss-of-function assays were performed to detect the biological functions of the target gene. At last, the rescue assays were used to investigate the relationship among lncRNA DLEU2, miRNA and target gene. Results: With the help of GEPIA analysis, we observed that lncRNA DLEU2 was up-regulated in EC tissues and associated with poor prognosis. Loss-of-function assay showed that silencing lncRNA DLEU2 inhibited the proliferation, migration and invasion of EC cells, and induced apoptosis by regulating the Bcl-2/Bax axis and Caspase cascade. Overexpression of lncRNA DLEU2 increased the proliferation, migration and invasion abilities of TE-1 cells, as well as decreased cell apoptosis. Bioinformatics analysis and dual-luciferase reporter assay verified that miR-30e-5p could directly bind with lncRNA DLEU2, and E2F7 was a direct target for miR-30e-5p in EC cells. Moreover, our data revealed that silencing E2F7 decreased the proliferation, migration and invasion abilities of EC cells, and induced apoptosis. Furthermore, the rescue assays demonstrated that the effects of lncRNA DLEU2 on the proliferation, migration and invasion of EC cells were reversed by miR-30e-5p inhibitor or up-regulation of E2F7. Conclusions: Our findings revealed the pro-oncogenic role of lncRNA DLEU2 and E2F7 in the progression of EC, suggesting that lncRNA DLEU2 exerts ceRNA functions in EC through regulating miR-30e-5p/E2F7 axis. 

Retracted: No

PubPeer comments:
 Figure 8B. The top panels (Eca-109 cells) appear to be the same as the bottom panels (KYSE-150 cells). Could the authors check if something went wrong during figure assembly, please? ![file] ,
Essential Oils as Antiviral Agents, Potential of Essential Oils to Treat SARS-CoV-2 Infection: An In-Silico Investigation
Authors: William N Setzer
Kendall G Byler
Joyce Kelly R da Silva
Pablo Luis Baia Figueiredo
Journal: International Journal of Molecular Sciences (2020)
Discipline: CHEMISTRY
Keywords: COVID−19; antiviral; corona virus; essential oils; molecular docking.
Affiliations: Laboratório de Biotecnologia de Enzimas e Biotransformações, Universidade Federal do Pará, Belém, PA 66075-900, Brazil., Departamento de Ciências Naturais, Centro de Ciências Sociais e Educação, Universidade do Estado do Pará, Belém, PA 66050-540, Brazil., Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, AL 35899, USA., Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA., Aromatic Plant Research Center, 230 N 1200 E, Suite 100, Lehi, UT 84043, USA.

Abstract:  Essential oils have shown promise as antiviral agents against several pathogenic viruses. In this work we hypothesized that essential oil components may interact with key protein targets of the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease (SARS-CoV-2 Mpro), SARS-CoV-2 endoribonucleoase (SARS-CoV-2 Nsp15/NendoU), SARS-CoV-2 ADP-ribose-1″-phosphatase (SARS-CoV-2 ADRP), SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp), the binding domain of the SARS-CoV-2 spike protein (SARS-CoV-2 rS), and human angiotensin-converting enzyme (hACE2). The compound with the best normalized docking score to SARS-CoV-2 Mpro was the sesquiterpene hydrocarbon (E)-β-farnesene. The best docking ligands for SARS-CoV Nsp15/NendoU were (E,E)-α-farnesene, (E)-β-farnesene, and (E,E)-farnesol. (E,E)-Farnesol showed the most exothermic docking to SARS-CoV-2 ADRP. Unfortunately, the docking energies of (E,E)-α-farnesene, (E)-β-farnesene, and (E,E)-farnesol with SARS-CoV-2 targets were relatively weak compared to docking energies with other proteins and are, therefore, unlikely to interact with the virus targets. However, essential oil components may act synergistically, essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms. 

Retracted: No

PubPeer comments:
 Figure 3D. * Red boxes: The blank and laser panels (assumed, no clear labeling) appear to look very similar * Blue boxes: The blank and laser panels (assumed, no clear labeling) appear to look very similar ![file] Paper in its current state archived here, because the journal has been known to make silent corrections without alerting its readers: https: web.archive.org web 20210210213306 https: www.jbuon.com archive 21-5-1068.pdf ,
METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion
Authors: Xiaojun Man
Guojun Zhang
Chuize Kong
Xiao Dong
Zhe Zhang
Bo Zhan
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: bladder cancer; METTL13; tumor suppressor; cell proliferation; cell migration
Affiliations: Department of Urology, the First Hospital of China Medical University, Shenyang, 110001, China., Department of Hematology, Shengjing Hospital of China Medical University, Shenyang City, 110022, China.

Abstract:  The incidence of bladder cancer has increased in the last few decades, thus novel markers for early diagnosis and more efficacious treatment are urgently needed. It found that METTTL13 protein is aberrant expression in variety of human cancers and METTL13 was involved in oncogenic pathways. However, the role of METTL13 has been unexplored in bladder cancer to date. Here, expression of METTL13 was lower in bladder cancer tissue samples and cancer cell lines than in normal bladder tissue and cell lines. METTL13 was downregulated in the late stages of the disease and was maintained at low level throughout the tumor progression process based on tumor node metastasis (TNM) staging. Further research suggested that METTL13 negatively regulates cell proliferation in bladder cancer and reinstates G1/S checkpoint via the coordinated downregulation of CDK6, CDK4 and CCND1, decreased phosphorylation of Rb and subsequent delayed cell cycle progression. Moreover, METTL13-dependent inhibition of bladder cancer cell migration and invasion is mediated by downregulation of FAK (Focal adhesion kinase) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation, β-catenin expression and MMP-9 expression. These integrated efforts have identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. 

Retracted: No

PubPeer comments:
 In Figure 6c, a micrograph has been duplicated and presented as something else. The presentation of tumors in Figure 6A is made up of separate micrographs of individual tumors. This is not the way to do it, in order to compare the tumor size. Not even a size marker is provided. ![file] ,