microRNA-526b servers as a prognostic factor and exhibits tumor suppressive property by targeting Sirtuin 7 in hepatocellular carcinoma
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Xin Liu1,*, Liu Yang1,*, Jianfeng Tu2,*, Wenwei Cai2, Meiqi Zhang2, Zhangxuan Shou3, Yingmin Yao4 and Qiuran Xu1
1Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province 310014, China
2Department of Emergency, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province 310014, China
3Department of Pharmacy, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province 310014, China
4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710061, China
*These authors have contributed equally to this work
Qiuran Xu, email: [email protected]
Yingmin Yao, email: [email protected]
Keywords: miR-526b, HCC, tumor growth, metastasis, SIRT7
Received: July 12, 2017 Accepted: August 27, 2017 Published: September 23, 2017
Recent studies have reported that microRNA-526b (miR-526b) is implicated in the growth and metastasis of cancer cells. However, the clinical significance of miR-526b and its role as well as underlying mechanisms are largely unknown in hepatocellular carcinoma (HCC). Here, we detected miR-526b expression difference between HCC and matched nontumor tissues with qRT-PCR. We found that miR-526b displayed lower expression in HCC patient tissues and cells. Clinical analysis revealed that low miR-526b expression correlated with large tumor size, venous infiltration, advanced tumor-node-metastasis (TNM) stage. Furthermore, miR-526b underexpression independently predicted poor prognosis of HCC patients. Functionally, we demonstrated that miR-526b inhibited proliferation, migration and invasion of HCC cells in vitro. Moreover, miR-526b overexpression restrained the tumor growth and pulmonary metastasis in vivo. Mechanistically, we proved that miR-526b could directly bind to 3’UTR of sirtuin 7 (SIRT7) mRNA and repressed its expression. miR-526b and SIRT7 showed a negative correlation in HCC tissues. More importantly, up-regulating SIRT7 expression antagonized miR-526b-inhibited proliferation, migration and invasion in SMMC-7721 cells. Furthermore, miR-526b suppressed epithelial-to-mesenchymal transition (EMT) of HCC cells. Immunoblotting analysis indicated that miR-526b reduced the levels of phosphorylated ERK (p-ERK), c-Myc, Cyclin D1, c-Jun, SNAIL and SLUG in HCC cells. SIRT7 restoration promoted phosphorylation of ERK and EMT in miR-526b overexpressing SMMC-7721 cells. Taken together, this is the first time we demonstrated that miR-526b might function as a prognostic biomarker and suppressed SIRT7 expression, and subsequently led to the growth and metastasis of HCC. Our findings provide miR-526b/SIRT7 axis as a promising drug target for HCC.
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