miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN
Authors: Kai Liu
Baoxing Jia
Ludong Tan
Songyang Liu
Zhe Jin
Wei Zhang
Yahui Liu
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-494; oncomiR; tumor development; progression; metastasis
Affiliations: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, P.R. China.

Abstract:  MicroRNA-494 (miR-494) acts as an oncomiR and is involved in tumor development, progression and metastasis, and confers resistance to chemotherapeutic drugs by targeting a number of molecules in several human cancers. However, the function and underlying molecular mechanism of miR-494 in hepatocellular carcinoma (HCC) has not been totally elucidated. In the present study, we determined the role played by miR-494 in HCC tissues and HCC cell lines using quantitative RT-PCR (RT-qPCR). The results showed that, miR-494 was significantly upregulated in HCC tissues and HCC cell lines. Additionally, a high miR-494 expression positively correlated with tumor differentiation (P&lt;0.01), TNM stage (P&lt;0.01) and lymph node metastasis (P&lt;0.01). Luciferase reporter assays confirmed that miR-494 binds to the 3'-untranslated region (3'-UTR) of the phosphatase and tensin homolog (PTEN) mRNA and represses its translation. Functional analyses indicated that the upregulation of miR-494 promoted cell viability, migration and invasion, decreased cell apoptosis and cell cycle arrest at G1 stage, and conferred sorafenib resistance to HCC cell lines. Underexpression of PTEN by siRNA significantly attenuated the inhibitory effects of anti-miR-494 on the proliferation, migration and invasion of liver cancer cells. Mechanistic investigations revealed that miR-494 suppressed the expression of PTEN but increased the expression of PI3K and p-Akt, which contribute to the promotion of proliferation, migration and invasion, and increased sorafenib resistance to HCC cell lines. These findings suggested that miR-494 is a potential candidate for HCC therapeutics. 

Retracted: Yes

PubPeer comments:
 Fig 6.  PI3K AKT signaling pathway inactivation is associated with PTEN expression. PTEN protein and the downstream genes PI3K and phosp-AKT protein expression were determined in HCC cells after transfection with miR-494 mimic or anti-miR-494 . ![file] Colored rectangles are to mark similarities to *[left]* Fig 5C of [Song et al (2015)] .  Western blotting of EGFR protein expression in the HeLa cells after transfection with the miR-133a mimic or miR-Ctrl. u03b2-actin was used as an internal control. *[right]* Fig 3c from [Zhang et al (2015)] .  The expression levels of MMP-2 and MMP-9 were determined by Western blot after being transfected with miR-133a or miR-NC. GAPDH was used as internal control . ![file] , 
 Figs 3C,E.  The ... (C) protein expression levels of PTEN were detected in the HCC cells after transfection with miR-494 mimic or inhibitor. The PTEN protein expression level was detected in... (E) HCC cell lines by western blotting. ![file] Loading control band in the blue rectangle is surprisingly similar to *[above]* Fig 5D from [Liu et al (2016)] .  The ADAM10 protein expression was measured in four HCC cell lines (SMMC-7721, Hep3B, HepG2, Huh-7) and normal hepatic cell line HL-7702 by western blot . *[below]* Fig 4D of [Dong et al (2016)] . ![file] , 
 #2 *[right]* Figs 3C,E again.  The ... (C) protein expression levels of PTEN were detected in the HCC cells after transfection with miR-494 mimic or inhibitor. The PTEN protein expression level was detected in... (E) HCC cell lines by western blotting. *[left]* Fig 3C from [Ge et al (2016)] .  Western blot analysis of uPA, MMP-2 and MMP-9 protein expression following transfection with miR-497 mimic or miR-control. GAPDH was used as an internal control . I have concerns. ![file] , 
 #1 *[right]* Fig 6 again. *[left]* Fig 7 from [Xia, Li Lv (2016)] .  miR-107 inhibits the PI3K AKT signal pathway. PI3K, p-PI3K, AKT and p-AKT protein expression was detected in A549 cells transfected with miR-107 mimic miR-NC or si-BDNF si-NC by western blotting. u03b2-actin was used as the internal control. ![] , 
 Retracted [30 December 2021] . ---------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that the western blotting data in Figs. 3 and 6 were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,