研究显示：5'-非翻译区N6-甲基腺嘌呤(m6A)修饰可促进蛋白翻译；而环状RNA(circRNA)能通过与RNA结合蛋白相互作用，调控亲本基因表达。我们发现：胃癌中肝素酶(HPSE)外显子生成的circ-HPSE能结合RNA结合基序蛋白8A(RBM8A)，阻遏RBM8A招募RNA甲基化酶3(METTL3)至HPSE的5'-非翻译区，抑制m6A修饰及HPSE蛋白翻译。据此，本研究拟深入解析RBM8A、METTL3对胃癌中HPSE的5'-非翻译区m6A修饰及蛋白翻译的调控作用；明确RBM8A与circ-HPSE、METTL3相互作用的结构域；观测circ-HPSE对RBM8A招募METTL3至调控位点、m6A修饰及HPSE表达的影响；观测过表达/敲低circ-HPSE、回补HPSE表达或RBM8A功能对胃癌侵袭转移的调控作用，从环状RNA角度阐明HPSE表达调控机理，为胃癌的治疗提供新思路。

Previous studies reveal that the N6-methyladenosine (m6A) modification within 5'-untranslated region facilitates protein translation, while circular RNA (circRNA) is able to regulate the expression of parental gene through interacting with RNA binding protein. Our results indicated that in gastric cancer, circRNA derived from exons of heparanase (circ-HPSE) was able to interact with RNA binding motif protein 8A (RBM8A) and block its recruitment of RNA methyltransferase like 3 (METTL3) on the 5'-untranslated region of HPSE, resulting in suppression of m6A modification and HPSE protein translation. Therefore, this study will further elucidate the effects of RBM8A and METTL3 on the m6A modification within 5'-untranslated region and protein translation of HPSE in gastric cancer. The domains essential for the interaction of RBM8A with circ-HPSE and METTL3 will be explored. The impacts of circ-HPSE on RBM8A-recruited METTL3 enrichment on regulatory sites, m6A modification, and HPSE expression will be studied in gastric cancer. Through ectopic expression or knockdown of circ-HPSE and rescue of HPSE levels or RBM8A function, the changes in the invasion, metastasis, and angiogenesis of gastric cancer cells will be detected in vitro and in vivo. This study will define the roles and mechanisms of circRNA in regulating the expression of HPSE, and will provide a novel strategy for the treatment of gastric cancer.