Effects of miR-155 on proliferation and apoptosis by regulating FoxO3a/BIM in liver cancer cell line HCCLM3
Authors: W-W Liao
C Zhang
W-J Wang
F-R Liu
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MiR-155; FoxO3a; BIM; HCC; apoptosis
Affiliations: Department of Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. .

Abstract:  Objective: MiR-155 has been shown to be up-regulated in hepatocellular carcinoma (HCC) patients. B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (BIM) regulates cell proliferation and apoptosis, as its down-regulation is involved in HCC onset. Transcriptional factor FoxO3a mediates BIM expression and is related to HCC pathogenesis. Bioinformatics analysis showed targeted regulation of FoxO3a by miR-155. This study aims to investigate whether miR-155 plays a role in mediating FoxO3a/BIM signal pathway and HCC occurrence. Patients and methods: HCC patients were collected for tumor and adjacent tissues, in which microRNA-155 (miR-155) and FoxO3a expressions were examined. In vitro cultured HCCLM3, HepG2 and L-02 cells were tested for basal apoptotic rate by flow cytometry and were compared for miR-155 and FoxO3a expression. Dual-luciferase reporter gene assay demonstrated the targeted relationship between miR-155 and FoxO3a. HCCLM3 cells were treated with miR-155 inhibitor and/or FoxO3a-pMD18-T. Cell apoptosis and proliferation were examined by using flow cytometry and MTT assays, respectively. Western blot and spectrometry assay were employed to quantify the FoxO3a, BIM expressions, and caspase activity. Results: Compared to adjacent tissues, HCC tissues had significantly higher miR-155 and significantly lower FoxO3a expression (p&lt;0.05). HCCLM3 and HepG2 cells had significantly lower FoxO3a expression and basal apoptotic rate compared to L02 cells, whilst miR-155 level was significantly higher (p&lt;0.05). MiR-155 targeted and inhibited 3'-UTR of FoxO3a, increasing BIM expression, caspase-3, and caspase-9 activities, and enhancing cell apoptosis and weakening proliferation. Conclusions: HCC tissues elevated the miR-155 and suppressed the FoxO3a expressions. MiR-155 targeted and inhibited FoxO3a expression to suppress the BIM, depress caspase-3 and caspase-9 activities, therefore inhibiting the HCC cell apoptosis and facilitating proliferation. 

Retracted: Yes

PubPeer comments:
 This is the retraction notice for DOI: 10.26355 eurrev_201803_14468, found at: https: www.europeanreview.org article 21845 See: https: pubpeer.com publications 494D8944525EEC0DB50F6D0557D342 The journal writes:  *The article u201cEffects of miR-155 on proliferation and apoptosis by regulating FoxO3a BIM in liver cancer cell line HCCLM3, by W.-W. Liao, C. Zhang, F.-R. Liu, W.-J. Wang, published in Eur Rev Med Pharmacol Sci 2018; 22 (5): 1277-1285. DOI: 10.26355 eurrev_201803_14468. PMID: 29565484.u201d has been withdrawn from the authors.* * The Publisher apologizes for any inconvenience this may cause.* It is unfortunate, and not according to COPE guideline, that the journal has removed the PDF. Luckily, the PDF was captured by the WayBackMachine, and can be found here: https: web.archive.org web 20200215102933 https: www.europeanreview.org wp wp-content uploads 1277-1285-1.pdf It appears to be part of the Paper Mill #2, AKA the Paint It Black Paper Mill, described by Smut Clyde on Leonid Schneider s blog For Better Science: https: forbetterscience.com 2020 02 27 dark-satanic-papermills Here is part of Figure 2 as an illustration of the pitch black Western blots and particular shape of the flow cytometry plots.  , 
 #1 The publisher has restored the PDF in watermarked form, so kudos to them,  ,