LncRNA POU6F2-AS2 contributes to malignant phenotypes and paclitaxel resistance by promoting SKP2 expression in stomach adenocarcinoma

Abstract

This study aimed to investigate the role and mechanism of POU6F2-AS2 in the development of gastric cancer. POU6F2-AS2 expression was considerably higher in clinical stomach adenocarcinoma (STAD) tissues and gastric cancer cell lines (MKN-28 and MGC-803) than in neighbouring normal tissues and gastric mucosa epithelial cells (GES-1). POU6F2-AS2 overexpression resulted in a low overall survival probability, progression-free survival probability and post progression survival probability, as well as increased cell viability, migration and invasion of gastric cancer cells, thereby inhibiting apoptosis. Based on RNA pull-down, cycloheximide and MG132 incubation experiments, POU6F2-AS2 promoted SKP2 by stabilizing NONO expression. In addition, in vivo silencing of POU6F2-AS2 in gastric cancer cells can inhibit tumour progression and produce a synergistic antitumour effect when combined with paclitaxel. POU6F2-AS2 is overexpressed in STAD, which is attributed to a bad prognosis. In vitro and in vivo experiments have confirmed that the POU6F2-AS2/NONO/SKP2 axis promotes STAD progression, and that the silencing of POU6F2-AS2 plays a synergistic antitumour effect when combined with paclitaxel. Therefore, POU6F2-AS2 may be potentially developed as a target to inhibit STAD and reduce chemoresistance.

Keywords:

• Stomach adenocarcinoma
• LncRNA POU6F2-AS2
• NONO
• SKP2
• paclitaxel
• chemoresistance
• bioinformatic analysis

Disclosure statement

The authors have no conflicts of interest to declare.

Ethics statement

All animal experiments were approved by the Second Affiliated Hospital of Nanchang University Experimental Animal Ethics Committee.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.