PITPNA-AS1/miR-98-5p to Mediate the Cisplatin Resistance of Gastric Cancer

PITPNA-AS1/miR-98-5p介导胃癌顺铂耐药

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作者:Zhongling Ma, Gang Liu, Suhong Hao, Tianfu Zhao, Wei Chang, Jiansheng Wang, Hong Ren, Xinhan Zhao

Abstract

Gastric cancer (GC) is the most deadly gastrointestinal malignancy with high incidence and mortality. Although, molecular mechanisms which drive gastric cancer progression are extensively investigated, the roles of long noncoding RNA (lncRNA) in gastric cancer growth and drug sensitivity remain unclear. Platinum is a mainstay to treat gastric cancer, and platinum resistance always leads to the local recurrence of gastric cancer. Therefore, it is important to identify biomarkers or therapeutic targets to sensitize gastric cancer to platinum. In this study, we employ noncoding RNA sequencing and found that lncRNA PITPNA-AS1 is overexpressed in gastric cancer tissues and associated with poor survival of gastric cancer patients. Kockdown of PITPNA-AS1 in gastric cancer cells significantly inhibited cell growth and triggered apoptotic cell death in gastric cancer cells. Also, cisplatin treatment could decrease PITPNA-AS1 levels in gastric cancer cells through inhibiting H3K27ac. Besides, PITPNA-AS1 is elevated in cisplatin-resistant gastric cancer cells and tissues, PITPNA-AS1 knockdown could sensitize gastric cancer cells to cisplatin treatment. Furthermore, we identified that PITPNA-AS1 directly interacts and inhibits miR-98-5p. Therefore, PITPNA-AS1 could be served as a potential biomarkers and curative therapeutic targets for gastric cancer progression.

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