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