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MicroRNA-106b-5p 通过调节 FOG2 促进肝细胞癌的发展
Authors Yu LX, Zhang BL, Yang MY, Liu H, Xiao CH, Zhang SG, Liu R
Received 29 January 2019
Accepted for publication 20 April 2019
Published 15 July 2019 Volume 2019:12 Pages 5639—5647
DOI https://doi.org/10.2147/OTT.S203382
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Shreya Arora
Peer reviewer comments 2
Editor who approved publication: Dr Carlos E Vigil
Background: A recent study has revealed that miR-106b-5p might promote hepatocellular carcinoma (HCC) stemness maintenance and metastasis by targeting PTEN via PI3K/Akt pathway based on HCC cell lines and animal models. Its clinical relevance remains unknown.
Purpose: Herein, we aimed to evaluate associations of miR-106b-5p dysregulation with various clinicopathological features of HCC patients and investigate its functions during HCC progression.
Patients and methods: At first, miR-106b-5p expression in 130 pairs of HCC and adjacent normal liver tissues was detected by quantitative PCR. Chi-square test was then performed to determine clinical significance. Further investigations on its functions were performed by miRNA target prediction and validation, as well as cellular experiments.
Results: miR-106b-5p levels in HCC tissues were significantly higher than those in the adjacent normal liver tissues (P <0.001). High miR-106b-5p expression was significantly associated with advanced tumor stage (P =0.02) and high tumor grade (P =0.03). In addition, Friend of GATA 2 (FOG2) was identified as a direct target of miR-106b-5p in HCC cells. Moreover, the clinical relevance to HCC progression of the combined high miR-106b-5p and low FOG2 expression was more significant than high miR-106b-5p alone. Functionally, enforced expression of miR-106b-5p reduced FOG2 expression and promoted the proliferation and invasion of HCC cells. Furthermore, co-transfection of FOG2 restored the oncogenic roles of miR-106b-5p over-expression.
Conclusion: Our data offer the convincing evidence that miR-106b-5p upregulation may promote the aggressive progression of HCC. miR-106b-5p overexpression may promote HCC cell proliferation and invasion by suppressing FOG2, implying its potentials as a promising therapeutic target for HCC patients.
Keywords: hepatocellular carcinoma, microRNA-106b-5p, friend of GATA 2, tumor progression, prognosis