Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma

Abstract

MicroRNA-372 (miR-372) has been demonstrated to play a crucial role in cellular proliferation and apoptosis of cancer cells. However, its effects in hepatocellular carcinoma (HCC) have not been explored. The aim of this study was to investigate the clinical significance of miR-372 in human HCC. Quantitative RT-PCR was performed to detect miR-372 expression in HCC clinical samples and cell lines. Then, Kaplan-Meier and Cox proportional regression analyses were performed to determine the association of miR-372 expression with survival of HCC patients. Moreover, the effects of miR-372 on tumorigenicity of HCC cell lines were evaluated by in vitro assays. miR-372 expression in HCC tissues was significantly higher than in the corresponding normal adjacent liver tissues (P < 0.001). There was a correlation between miR-372 upregulation and advanced TNM stage of HCC patients (P = 0.02). In addition, HCC patients with higher miR-372 expression had significantly poorer recurrence-free survival (P = 0.006) and overall survival (P = 0.001). Multivariate analysis revealed that high miR-372 expression was an independent predictor of poor prognosis (for recurrence-free survival: Hazard Ratio [HR] 6.826, P = 0.01; for overall survival: HR 9.533, P = 0.008). Moreover, in vitro assays demonstrated that the ectopic expression of miR-372 may significantly promote the cellular proliferation, invasion, and migration of HCC cell lines. Our findings showed that miR-372 may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. Furthermore, miR-372 has been identified as a promoter for tumorigenicity of HCC cells, suggesting that it might be a prospective therapeutic target for HCC.

YY1-MIR372-SQSTM1 regulatory axis in autophagy

“…However, MIR372 was upregulated and predicts poor prognosis in hepatocellular carcinoma, indicating the same microRNA might have different functions in various tissues. 43 In addition, the same mRNA might be targeted by various microRNAs. Indeed, other microRNAs including MIR106a were predicted to regulate SQSTM1 expression.…”

The role of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma

“…Wang et al, 2010). miR-372 has been shown to be involved in regulation of cell cycle, apoptosis, invasion, and proliferation in many types of human cancers (Gu, Guo, Zou, Zhu, & Zhang, 2013;Lai et al, 2012;Li et al, 2013;Wu et al, 2015). Inhibiting miR-372 function reduced translational repression of its target to effect phosphorylation and activation of cyclic adenosine monophosphate responsive element binding protein (CREB) (J.…”

Blocking of STAT3 activation by miR-491, acting via EGFR, is involved in metastasis of hepatocellular carcinoma cells through inhibiting cancer stem cell-like properties

“…They also regulate the expression of oncogenes and tumor suppressors [8]. Many miRNAs, for example, miR-17, miR-21, and miR-373, are up-regulated in cancers and may function as oncogenes [9][10][11]. In HCCs, miR-122, miR-199a-5p, and miR-221 are regarded as tumor suppressors [12][13][14].…”