Oncotarget

Research Papers:

MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation

Jianxin Jiang, Yi Zhang, Yuting Guo, Chao Yu, Meiyuan Chen, Zhu Li, Se Tian and Chengyi Sun _

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Oncotarget. 2015; 6:6359-6372. https://doi.org/10.18632/oncotarget.3438

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Abstract

Jianxin Jiang1,*, Yi Zhang2,*, Yuting Guo1, Chao Yu1, Meiyuan Chen1, Zhu Li1, Se Tian1 and Chengyi Sun1

1 Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, China

2 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China

* These authors contributed equally to this work

Correspondence to:

Chengyi Sun, email:

Keywords: Hepatocellular carcinoma, miR-3127, PI3K/AKT pathway, PHLPP, INPP4A

Received: November 09, 2014 Accepted: January 21, 2015 Published: January 31, 2015

Abstract

Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT signaling pathway. Here we demonstrated that, by suppressing multiple phosphatases, miR-3127 promotes growth of hepatocellular carcinoma (HCC). Our study also reveals clinical significance of miR-3127 expression in HCC patients. MiR-3127 expression was markedly upregulated in HCC tissues and cells. Furthermore, high miR-3127 expression was associated with an aggressive phenotype and poor prognosis. MiR-3127 overexpression promoted HCC cell proliferation in vitro and tumor growth in vivo. Also, miR-3127 accelerated G1-S transition by activating AKT/ FOXO1 signaling, by directly targeting the 3′ untranslated regions (3`UTR) of pleckstrin homology domain leucine-rich repeat protein phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their expression. In agreement, the miRNA antagonist antagomir-3127 suppressed HCC cell proliferation and tumor growth by inhibiting the AKT/FOXO1 signaling. Taken together, these findings suggest that silencing miR-3127 might be a potential therapeutic strategy.


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