MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

Molecular Cancer

Research

Jianfeng Tu¹  Lijie Li²  Zhenyu Zhou³  Zhikui Liu⁴  Kangsheng Tu⁴  Yufeng Wang⁴  Xin Liu⁵  Qiuran Xu⁶  Liu Yang⁶  Hangxing Bao⁷ 

[1] Department of Emergency, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), 310014, Hangzhou, Zhejiang Province, China;Department of Gynecology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), 310014, Hangzhou, Zhejiang Province, China;Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120, Guangzhou, Guangdong Province, China;Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, Shaanxi Province, China;Department of Neurosurgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), 310014, Hangzhou, Zhejiang Province, China;Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), 310014, Hangzhou, Zhejiang Province, China;Zhejiang Hospital of Traditional Chinese Medical, 310006, Hangzhou, Zhejiang Province, China;

关键词: MicroRNA-1296;    Hepatocellular carcinoma;    SRPK1;    Metastasis;    PI3K/AKT pathway;   

DOI  :  10.1186/s12943-017-0675-y

 received in 2017-03-14, accepted in 2017-06-06,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIncreasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown.MethodsThe levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay.ResultsWe found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296.ConclusionsUnderexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.

【 授权许可】

CC BY   
© The Author(s). 2017