关键词: HOXC-AS3, miR-15b-5p, E2F3

Abstract: Background and purpose: Gastric cancer is a malignant tumor with high morbidity and mortality. Long non-coding RNA (lncRNA) is a kind of regulatory macromolecular non-coding RNA and plays an important role in the metastasis of gastric cancer. This study aimed to explore the expression profile of lncRNA HOXC-AS3 (lnc-HOXC-AS3) and the molecular mechanisms of lnc-HOXC-AS3 in promoting the proliferation and metastasis of human gastric cancer via regulating the miR-15b-5p/E2F3 axis. Methods: We discovered the abnormal lncRNA expression in gastric cancer tissues acquired from 90 patients treated in the First Affiliated Hospital of Anhui Medical University from Apr. 2017 to Dec. 2018 by bioinformatic analysis and selected the lnc-HOXC-AS3 for the further study. First, we detected the expression of lnc-HOXC-AS3 in gastric cancer by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Then, the effect of lnc-HOXC-AS3 on proliferation and migration of gastric cancer cells (MGC803) was determined by cell counting kit-8 (CCK-8) and transwell assays. Finally, the interaction and regulation of lnc-HOXC-AS3, miR-15b-5p and E2F3 were explored using dual-luciferase reporter gene assay. Results: Lnc-HOXC-AS3 was obviously upregulated in gastric cancer. Loss-and gain-of-function assays indicated that lnc-HOXC-AS3 inhibited proliferation and migration of gastric cancer cells in vitro. Mechanistic analysis demonstrated that miR-15b-5p was a direct target of lnc-HOXC-AS3 in gastric cancer. Moreover, E2F3 was identified as a direct target of miR-15b-5p, and lnc-HOXC-AS3 could bind to miR-15b-5p, which relieved the inhibitive effect of miR-15b-5p on E2F3 and promoted the proliferation and migration of gastric cancer cell. Conclusion: Lnc-HOXC-AS3 is abnormally upregulated in gastric cancer and can promote the proliferation and migration of gastric cancer cells by regulating miR-15b-5p/E2F3 axis, which indicates that lnc-HOXC-AS3 may serve as a novel prognostic biomarker and therapeutic target in gastric cancer.

Key words: HOXC-AS3, miR-15b-5p, E2F3