Long noncoding RNA ZFPM2-AS1 regulates ITGB1 by miR-1226-3p to promote cell proliferation and invasion in hepatocellular carcinoma

W. Liu, G.-Q. Zhang, D.-Y. Zhu, L.-J. Wang, G.-T. Li, J.-G. Xu, X.-L. Jin, Y.-M. Zhu, X.-Y. Yang

Department of Infectious Diseases, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China. gqzhang2019@yeah.net

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• Oncology

OBJECTIVE: Long noncoding RNA (lncRNA) is emerging as a vital regulator in various tumors. However, the biological function of ZFPM2-antisense RNA 1 (ZFPM2-AS1) in hepatocellular carcinoma (HCC) remains unclear. The present study aims to explore the function and mechanism of ZFPM2-AS1 in hepatocellular carcinoma progression.

PATIENTS AND METHODS: The ZFPM2-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Effects of ZFPM2-AS1 on tumor cell proliferation and invasion were detected by CCK8 assay or EdU assay or matrigel migration assay and Western blot. The Luciferase reporter assay, RNA pulldown assay, qRT-PCR, and Western blot were performed to explore and confirm the interaction between ZFPM2-AS1 and miR-1226-3p and integrin β1 (ITGB1).

RESULTS: ZFPM2-AS1 was overexpressed in HCC tissues and cell lines. High levels of ZFPM2-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. ZFPM2-AS1 knockdown inhibited cell proliferation and invasion. ZFPM2-AS1 could directly bind to and negatively regulate miR-1226-3p expression. Moreover, ITGB1 was identified as a target gene of miR-1226-3p. ITGB1 was found to be directly negatively regulated by miR-1226-3p and indirectly upregulated by ZFPM2-AS1. Rescue assays demonstrated that ZFPM2-AS1 promotes HCC cell proliferation and invasion through modulating miR-1226/ITGB1 axis.

CONCLUSIONS: ZFPM2-AS1 promotes cell proliferation and migration by regulating miR-1226-3p/ITGB1 axis in HCC.

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