MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2

Zhang,Li; Wang,Wei; Li,Xiaobin; He,Sai; Yao,Jianfeng; Wang,Xiaolong; Zhang,Di; Sun,Xuejun

doi:10.3892/ijo.2016.3465

MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2

Authors:
- Li Zhang
- Wei Wang
- Xiaobin Li
- Sai He
- Jianfeng Yao
- Xiaolong Wang
- Di Zhang
- Xuejun Sun
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Affiliations: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Breast Cancer Program, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, P.R. China, Department of General Surgery, Shanxi Province People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: March 30, 2016 https://doi.org/10.3892/ijo.2016.3465
Pages: 2425-2434

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Abstract

Aberrant expression of microRNA-155 (miR-155) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR‑155 and its underlying mechanisms involved in hepatocarcinogenesis remain to be determined. In this study, we demonstrated that the expression of miR-155 was elevated in both hepatocellular carcinoma (HCC) tissues and cell lines. Clinical association analysis revealed that high expression of miR-155 was correlated with malignant clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading and TNM tumor stage. Furthermore, its high expression conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Gain- and loss-of function studies revealed that miR‑155 promoted cell cycle progression, cell proliferation and inhibited apoptosis. Mechanistically, we identified AT-rich interactive domain 2 (ARID2) as a direct downstream target and functional mediator of miR‑155 in HCC cells. Notably, alterations of ARID2 expression abrogated the effects of miR‑155 on HCC cell proliferation, cell cycle and apoptosis. Moreover, we demonstrated that Akt phosphorylation is essential for the functional roles of miR‑155 through altering Cyclin D1 and p27, which were key components of cell cycle machinery. Finally, we disclosed that the downregulation of miR‑155 suppressed tumor growth of HCC by inhibiting Akt signaling pathway. In conclusion, our results indicate that miR‑155 promotes tumor growth of HCC by targeting ARID2-mediated Akt phosphorylation pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.

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