MicroRNA-122 affects cell aggressiveness and apoptosis by targeting PKM2 in human hepatocellular carcinoma
Authors: Meiqi Zhang
Qiuran Xu
Xin Liu
Jianfeng Tu
Linxiao Pang
Wenwei Cai
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Human hepatocellular carcinoma; HCC; MicroRNAs; miR-122; Tumor suppressor
Affiliations: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China., Department of Neurosurgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

Abstract:  Human hepatocellular carcinoma (HCC) is a highly invasive tumor with frequent distant metastasis, which is the main cause for the poor prognosis. However, the mechanisms for metastasis remain poorly investigated. MicroRNAs (miRNAs) have been implicated in HCC progression. MicroRNA-122 (miR-122) is considered as a tumor suppressor in human cancer. In the present study, miR-122 expression was found to be significantly lower in HCC than the level in normal tumor-adjacent tissues. miR-122 was clearly silenced or downregulated in five HCC cell lines (HepG2, Hep3B, MHCC97H, Huh7 and SMMC-7721) compared with normal hepatocytes (LO2). HCC patients with low expression of miR-122 had a poor 3-year survival. Univariate analysis and multivariate Cox regression analysis indicated that miR-122 is an independent prognostic factor in HCC. Downregulation of miR-122 promoted proliferation and inhibited apoptosis in Hep3B cells. We found that the public miRNA database (TargetScan) predicted that PKM2 may be a target for miR-122, and the 3'-untranslated region (3'-UTR) of PKM2 contains a highly conserved binding site for miR-122. To identify this, pre-miR-122/anti-miR-122 were respectively transfected into the Hep3B cell line. We found that miR-122 overexpression significantly reduced the level of PKM2. Moreover, knockdown of PKM2 significantly increased miR-122 inhibitor-mediated Hep3B cell apoptosis and reduced miR-122 inhibitor-mediated Hep3B cell migration and invasion. Moreover, re-expression of PKM2 partially abrogated miR-122-induced HCC cell growth arrest and apoptosis in vivo. In conclusion, miR-122 serves as a prognostic biomarker and induces apoptosis and growth arrest by downregulating PKM2 in HCC. 

Retracted: No

PubPeer comments:
 Figures 6 and 7 appear to have overlapping images. ![file] ![file] , 
 Corrigendum [6 May 2021] . Following the publication of the above article, an interested reader drew to the authorsu2019 attention that Figs. 6C and 7A apparently contained overlapping panels, suggesting that these data for purportedly different experiments had been derived from the same original source. The woundu2011healing result for the antiu2011miRu2011122+siRNA PKM2 experiment in the lower panel of Fig. 6C and the transwell invasion result for the antiu2011miRu2011122+siRNA PKM2 experiment in Fig. 7A were erroneously selected. Accordingly, the authors repeated these assays and were able to confirm that the results were in accordance with the published results. Consequently, the corrected versions of Figs. 6 and 7, containing the replacement data for Figs. 6C and 7A, are shown opposite. It should be emphasized that the inadvertent errors that occurred during the compilation of these figures did not affect the research results or the conclusions of this article. The authors all agree to this Corrigendum, and are grateful to the Editor of *Oncology Reports* for allowing them to have the opportunity to correct these errors. The authors also apologize to the readership for any inconvenience these errors may have caused. ![] ![] , 
 Fig 7A (corrected version): ![] - *[left]* Fig 3C from  MicroRNA-130b promotes cell aggressiveness by inhibiting peroxisome proliferator-activated receptor gamma in human hepatocellular carcinoma ([Tu et al 2014] ). - *[right]* Fig 3B,D (Invasion panels) from  Fibulin-5 inhibits hepatocellular carcinoma cell migration and invasion by down-regulating matrix metalloproteinase-7 expression ([Tu et al 2014] ). ![] , 
 Fig 5A,C. A flow-cytometry panel appears twice, with different descriptions - red retangle. ![file] Green box: see - *[left]* Fig 3D from  FBXW7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma ([Li et al 2015] ). - *[upper right]* Fig 4 from  microRNA-497 inhibits cell proliferation and induces apoptosis by targeting YAP1 in human hepatocellular carcinoma ([Zhang et al 2016] ). - *[lower right]* Fig 4D from  Forkhead box protein A1 is a prognostic predictor and promotes tumor growth of gastric cancer ([Ren et al 2015] ). ![file] , 
 #4 Zhang et al. (2016) have admitted to manipulating images and applied for retraction ![file] ,