lncRNA HOXB-AS3 promotes hepatoma by inhibiting p53 expression

X.-M. Zhang, H. Chen, B. Zhou, Q.-Y. Zhang, Y. Liao, J.-S. Wang, Z.-H. Wang

Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China. wangzhaohong55@163.com

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• Oncology

OBJECTIVE: We investigate the mechanism of HOXB-AS3 in promoting the development of hepatocellular carcinoma.

PATIENTS AND METHODS: The expression of HOXB-AS3 in tumor tissues and adjacent tissues of hepatocellular carcinoma was detected by quantitative real time-polymerase chain reaction (qRT-PCR), and the relationship between the expression of HOXB-AS3 and tumor tissues was analyzed. The effects of HOXB-AS3 and p53 on cell proliferation, cell cycle and apoptosis were detected by plate cloning experiment and flow cytometry. The binding relationship between HOXB-AS3 and DNMT1 and the regulation mechanism of DNMT1 on p53 were tested by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) experiments, respectively. Western blot was used to detect the expression of p53 after knockdown of HOXB-AS3. The torsion experiment was performed to assess whether HOXB-AS3 regulated the proliferation and apoptosis of hepatoma cells by inhibiting p53 expression.

RESULTS: The results of qRT-PCR showed that the expression of HOXB-AS3 was significantly higher in cancerous tissues of patients with hepatocellular carcinoma than in adjacent tissues. The expression of HOXB-AS3 in patients in stage III and IV was significantly higher than that in stage I and II. Inhibition of HOXB-AS3 expression in liver cancer cells including Hep3B and LM3 could promote cell proliferation, inhibit cell apoptosis and induce cell cycle arrest in the G0/G1 phase. The results of RIP and ChIP experiments showed that HOXB-AS3 inhibited the expression of p53 by binding to DNMT1, and overexpression of p53 in Hep3B cells could partially reverse the changes in cell proliferation and apoptosis induced by HOXB-AS3.

CONCLUSIONS: Highly expressed HOXB-AS3 was confirmed to promote the proliferation of hepatocellular carcinoma cells and inhibit apoptosis, and the mechanism was related to the regulation role of HOXB-AS3 in p53 expression by binding to DNMT1.

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