RNA结合蛋白QKI介导UBA2外显子环状RNAs调控miR-142-5p/CYR61促进胃癌腹膜转移的机制研究

circRNA对胃癌腹膜转移的影响及分子机制尚未完全阐明。我们研究发现，在胃癌腹膜转移患者腹水外泌体中，UBA2外显子circRNAs: hsa_circ_0006211、hsa_circ_0050545、hsa_circ_0006186化疗后表达量显著下调，它们可能通过内源性竞争RNA机制抑制miR-142-5p对靶因CYR61的降解，进而促进胃癌的腹膜转移。另外，我们发现circRNA结合蛋白QKI能够促进hsa_circ_0006211、hsa_circ_0050545、hsa_circ_0006186生成。因此，我们提出假说：QKI介导的UBA2外显子circRNAs hsa_circ_0006211、hsa_circ_0050545、hsa_circ_0006186通过共同结合miR-142-5p，解除后者对CYR61翻译的抑制，从而促进胃癌腹膜转移。

The biological functions and molecular mechanism of circRNA in gastric cancer peritoneal metastasis are still unclear. We found that UBA2 exons circRNAs (hsa_circ_0006211, hsa_circ_0050545, hsa_circ_0006186) had significantly down-regulated expression after chemotherapy in the exosomes from ascites of gastric cancer patients with peritoneal metastasis. These circRNAs could target miR-142-5p by acting as an endogenous competitive RNA and inhibit miR-142-5p from degrading CYR61, which promotes peritoneal metastasis of gastric cancer. In addition, we found that the circRNA binding protein QKI could promote the generation of hsa_circ_0006211, hsa_circ_0050545, and hsa_circ_0006186. Therefore, we proposed the hypothesis that QKI-mediated UBA2 exon circular RNAs (hsa_circ_0006211, hsa_circ_0050545, hsa_circ_0006186) inhibit miR-142-5p from suppressing CYR61 translation by jointly sponging miR-142-5p, which thereby promoting peritoneal metastasis of gastric cancer.