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MicroRNA-302a-3p suppresses hepatocellular carcinoma progression by inhibiting proliferation and invasion

Authors Ye Y, Song Y, Zhuang J, Wang G, Ni J, Zhang S, Xia W

Received 3 March 2018

Accepted for publication 23 May 2018

Published 10 December 2018 Volume 2018:11 Pages 8175—8184

DOI https://doi.org/10.2147/OTT.S167162

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Ying Ye,1,* Yanan Song,1,* Juhua Zhuang,1 Guoyu Wang,1 Jing Ni,1 Suiliang Zhang,2 Wei Xia1

1Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Oncology Department, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Background: Involvement of microRNAs in tumor development and their potential as prognostic biomarkers had been well acknowledged. However, the expression, clinical significance, and functional mechanisms of microRNA (miR)-302a-3p in hepatocellular carcinoma (HCC) have not been reported.
Patients and methods: Real-time quantitative polymerase chain reaction was used to evaluate the expression of miR-302a-3p in 111 HCC tissues and adjacent normal liver tissues. Its association with clinicopathological characteristics was analyzed by the chi-square test. The Kaplan–Meier univariate survival analysis and multivariate Cox regression analysis were used to identify the clinical significance of miR-302a-3p in the overall survival (OS) of HCC patients. Transfection of miR-302a-3p mimics into HepG2 and Huh7 HCC cell lines was conducted to reveal its underlying mechanism in regulating HCC progression.
Results: miR-302a-3p expression was significantly decreased in HCC tissues compared with that in paired adjacent normal liver tissues (P=0.005). miR-302a-3p expression was correlated with tumor number (P=0.003), tumor size (P<0.001), and tumor TNM stage (P=0.028). The Kaplan–Meier survival analysis showed that patients in the high miR-302a-3p expression group had a better OS than those in the low miR-302a-3p expression group (P=0.002). Multivariate analysis confirmed that miR-302a-3p expression can be used as an independent predictor for HCC prognosis (HR=0.480, 95% CI=0.249–0.894, P=0.039). Proliferation, migration, and invasion capacities were all decreased in cells transfected with miR-302a-3p mimics. Moreover, our data showed a direct effect of miR302a-3p on inhibiting the expression and signaling of PRKACB in HCC cells.
Conclusions:
miR-302a-3p serves as a tumor suppressor in HCC progression by directly inhibiting tumor proliferation and invasion, and its low expression is a potential biomarker for predicting a poor prognosis of HCC patients.

Keywords: hepatocellular carcinoma, miR-302a-3p, invasion, prognosis, proliferation

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