Targeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cells
Authors: Y Wang
Y-R Zhao
Z-Z Wang
X Zhang
A-Y Zhang
J Ma
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Caspase-8; CFLAR; miR-20a; TRAIL; apoptosis
Affiliations: Infectious Disease Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. .

Abstract:  Objective: Elevated expression of caspase-8 (CASP8) and Fas-associating protein with a novel death domain (FADD)-like apoptosis regulator (CFLAR) increases sensitivity against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis, but with an unclear mechanism. A previous study showed decreased microRNA-20a (miR-20a) expression in hepatocellular carcinoma (HCC) patient's tumor tissues. Bioinformatics analysis showed potential targeting relationship between the 3-UTR of CFLAR and miR-20a. This study investigated if miR-20a played a role in regulating CFLAR expression and HCC apoptosis. Patients and methods: Expressions of miR-20a and CFLAR in model rat HCC tissues were compared to normal tissues. HCC patients were also collected for measuring miR-20a and CFLAR expressions between tumor and adjacent tissues. Dual-luciferase reporter gene assay was performed to evaluate the relationship between miR-20a and CFLAR. Cultured HepG2 cells treated with 120 ng/ml TRAIL were mixed with miR-20a mimic and/or si-CFLAR followed by measurement of Caspase-8/3 activity and cell apoptosis by flow cytometry, cell proliferation by MTT assay and protein expression by Western blot. Results: MiR-20a expression was significantly decreased in rat HCC tissues, while CFLAR was over-expressed. HCC patients had lower miR-20a level and higher CFLAR level in tumor tissues. MiR-20a targeted 3'-UTR of CFLAR to inhibit its expression. TRAIL remarkably up-regulated CFLAR expression, whilst inhibiting miR-20a expression and/or silencing CFLAR significantly potentiated caspase-8 and caspase-3 activity, enhanced sensitivity of HepG2 cells towards TRAIL-induced cell apoptosis, and decreased cell proliferative function. Conclusions: HCC had lower miR-20 and higher CFLAR expression. MiR-20a targeted and inhibited CFLAR expression, facilitated activation of caspase-8 and caspase-3, and enhanced sensitivity of HepG2 cells towards TRAIL-induced apoptosis, and subsequently reduced cell proliferation. 

Retracted: No

PubPeer comments:
 [Retracted] . No date provided. No reason provided. The article u201cTargeting of miR-20a against CFLAR to potentiate TRAIL-induced apoptotic sensitivity in HepG2 cellsu201d by Y. Wang, Y.-R. Zhao, A.-Y. Zhang, J. Ma, Z.-Z. Wang, X. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (9): 2087-2097 has been withdrawn. This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. It is possible that the retraction resulted from the evidence that the paper was a product from [a recognised papermill] , with Western Blots that were geometrical, sharp-edged black blobs on a featureless background... ![file] ...and flow-cytometry scatterplots that came from a limited repertoire, slightly customised with artisanal stippling. ![file] Other examples are listed in a Google document. https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit?usp=sharing As is common with this papermill, there is no obvious connection between the name of the nominal corresponding author and the email address provided. ![file] ,