MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis
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Recent studies have been shown that voltage-dependent anion channel 1 (VDAC1) plays an important role in carcinogenesis. However, its molecular biological function in hepatocellular carcinoma (HCC) has not been entirely clarified. This study investigated the expression of VDAC1 in HCC and its prognostic value for HCC patients. Furthermore, we also identify the relevant VDAC1 direct target. Western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemical (IHC) staining were performed to detect the expression of VDAC1 in HCC. Furthermore, the relationship between the VDAC1 level and clinicopathological features and prognostic values was explored. The effects of VDAC1 on HCC cell proliferation, migration, and invasion were also investigated in vitro. Predicted target gene of VDAC1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot analyses. Our results revealed elevated VDAC1 messenger RNA (mRNA) (P = 0.0020) and protein (P = 0.0035) expression in tumor tissue samples compared with paired adjacent non-tumorous tissue samples. High VDAC1 expression was correlated with distant metastasis (P = 0.025), differentiation (P = 0.002), and advanced tumor stage (P = 0.004) in HCC patients. Kaplan-Meier survival analysis demonstrated that high expression of VDAC1 was significantly correlated with a poor prognosis for HCC patients (P < 0.001). The multivariate analysis revealed that VDAC1 expression was an independent prognostic factor of the overall survival rate of HCC patients. Furthermore, knockdown of VDAC1 inhibits HCC cell proliferation, migration, and invasion in vitro. Moreover, further study revealed that miR-7 was a putative target of VDAC1. Our study suggested that miR-7 suppressed the expression of VDAC1. VDAC1 plays an important role in tumor progression and may be used as a potential role in the prognosis of HCC patients.
KeywordsVDAC1 Hepatocellular carcinoma Prognosis MiR-7
This study was supported by medical innovation team and talents of Jiangsu province (LJ201134).
Feiran Wang conceived of the study, performed the Western blot, qPCR analysis, and molecular studies, and drafted the manuscript. Yong Qiang participated in the design of the study and carried out the IHC analysis. Yasu Jiang and Yinda Wang collected the clinical data and tissue samples. Xian Shao and Lei Yin performed the statistical analysis. Zhong Chen participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Written informed consent was obtained from each patient and was approved by the Institute Research Ethics Committee at the Affiliated Hospital of Nantong University.
Conflicts of interest
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