Turkish Journal of Gastroenterology
Basic & Translational - Original Article

GABPA-Mediated Expression of HPN-AS1 Facilitates Cell Apoptosis and Inhibits Cell Proliferation in Hepatocellular Carcinoma by Promoting eIF4A3 Degradation

1.

Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

Turk J Gastroenterol 2019; 1: -
DOI: 10.5152/tjg.2024.23293
Read: 197 Downloads: 181 Published: 05 April 2024

Background/Aims: Hepatocellular carcinoma (HCC) represents a common neoplasm that presents a substantial worldwide health challenge. Nevertheless, the involvement of HPN-AS1 in HCC remains unknown.

Materials and Methods: The quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was utilized to measure HPN-AS1 expression in HCC. The GABPA effects on the HPN-AS1 promoter were analyzed through chromatin immunoprecipitation and luciferase reporter assays. Cell proliferation potential was determined by deploying CCK-8 assay, Ki-67 immunofluorescence staining, and colony formation assay. Cell apoptosis was detected using acridine orange/ethidium bromide staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Western blotting was utilized to measure the protein levels of proliferation factors and apoptosis regulators. HPN-AS1 binding to eIF4A3 was accessed by RNA-binding protein immunoprecipitation assay.

Results: HPN-AS1 was significantly downregulated in both HCC cells and tissues. Lower HPN-AS1 levels indicate a poorer HCC prognosis. Moreover, we found that GABPA functions as a transcription factor for HPN-AS1. Functional studies revealed that HPN-AS1 displayed inhibitory effects on HCC cell proliferation and promoted apoptosis. Mechanically, HPN-AS1 bound to and facilitated translation initiation factor eIF4A3 degradation. Loss of HPN-AS1 augmented eIF4A3 protein levels rather than eIF4A3 mRNA levels. Exogenous expression of eIF4A3 could restore eIF4A3 protein levels and reverse HPN-AS1 overexpression-induced cell proliferation inhibition and cell apoptosis.

Conclusion: Our study elucidated that HPN-AS1 downregulation was mediated by GABPA. HPN-AS acted as a tumor suppressor within HCC through binding and facilitating eIF4A3 degradation. The study provides a novel insight into the biological function of HPN-AS1 in HCC, suggesting that HPN-AS1 could be a promising biomarker and a potential target for HCC diagnosis and treatment.

Cite this article as: Hu Y, Sun X, Li BL, et al. GABPA-mediated expression of HPN-AS1 facilitates cell apoptosis and inhibits cell proliferation in hepatocellular carcinoma by promoting eIF4A3 degradation. Turk J Gastroenterol. Published online April 5, 2024. doi: 10.5152/tjg.2024.23293

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