CircCHAF1A induced cellular senescence by enhancing the stability of p21 to suppress gastric cancer progression

Circular RNA (CircRNAs) have been reported to play crucial roles in gastric Cancer pathogenesis. In previous research, we found that circCHAF1A was downregulated in gastric Cancer. However, the precise mechanisms and biological functions of circCHAF1A in gastric Cancer remain elusive. This study aims to investigate the regulatory role of circCHAF1A in gastric Cancer. We explored circCHAF1A's expression levels in gastric Cancer tissues and cell lines by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The functions were determined through cell counting, migration assays, cell cycle analysis, and cellular senescence assays. Mechanistic analysis was performed using RNA immunoprecipitation and luciferase reporter assays. Our results revealed a significant reduction of circCHAF1A, associated with poor prognosis and advanced TNM stage. Further experiments demonstrated that overexpression of circCHAF1A induced cellular senescence and inhibited cell proliferation in gastric Cancer cells. Mechanistically, circCHAF1A was found to Sponge miR-370-3p, thereby upregulating its target gene CDKN1A. Moreover, we found that circCHAF1A enhanced the stability of p21 message RNA, contributing to its prolonged half-life. Rescue experiments were conducted to validate the findings. These findings suggest that circCHAF1A induces cell senescence via the miR-370-3p/p21 axis, highlighting its potential as a novel therapeutic target for gastric Cancer treatment.

Cellular senescence; Gastric cancer; P21; circCHAF1A; miR-370-3p.