F10-AS1/hsa-miR-146b-5p/RAD54L axis regulates the progression of gastric cancer by mediating homologous recombination pathway

Abstract

Abstract Radiation resistance and the etiology of gastric cancer (GC) is significantly influenced by the DNA damage response, particularly DNA double-strand breaks (DSBs). A repair method for dealing with DNA damage is homologous recombination repair (HRR). The stability of the genome may be directly harmed by the homologous recombination deficiency (HRD) or blockage of the HRR pathway, inducing a slight increase in chromosome aberration and eventually leading to malignant tumors, including gastric adenocarcinoma. Therefore, to clarify the mechanism of DNA damage repair and create GC therapeutic targets, it is crucial to investigate the feedback mechanism of HRR to DSB in GC. Through bioinformatics analysis, the differentially expressed genes related to GC were found, the core genes were screened by the WGCNA method, the ceRNA network F10-AS1/hsa-miR-146b-5p / RAD54L was predicted and constructed by mirDIP and LncBase database, and the inhibitory effect of knockdown F10-AS1 on RAD54L was verified by in vivo and in vitro experiments. Results exhibited that knockdown of F10-AS1 raised the inhibitory effect of F10-AS1 on hsa-miR-146b-5p, promoted the combination of miR-146b-5p and RAD54L, downregulated the expression of RAD54L, and induced GAC cell death in vitro and slowed tumor growth in vivo. In the HR route of DNA repair, the F10-AS1/hsa-miR-146b-5p/RAD54 axis is crucial. Knockdown of F10-AS1 means that it inhibits homologous recombination in cancer cells and the maintenance efficiency of the DNA repair mechanism, induces the accumulation of spontaneous DSB, blocks DNA repair in cancer cells, achieves the best effect of anticancer drugs, and inhibits tumor development.