健脾清热活血方通过抑制METTL3介导的miR-196a-5p成熟调控胃癌细胞自噬的机制研究

胃癌发病率和死亡率均居恶性肿瘤第二位，中医药防治胃癌有一定的优势，但作用机制不完全明确。最新研究发现N6-甲基腺嘌呤（m6A）修饰介导的微小RNA（miRNA）成熟在胃癌的发生发展中具有重要作用，通过调控甲基转移酶样蛋白3（METTL3）介导的miRNA加工成熟，有可能是抑制胃癌发生发展的新途径。预实验结果显示：健脾清热活血方能抑制胃癌细胞的恶性行为、裸鼠皮下成瘤能力，并能调控METTL3、miR-196a-5p的表达。本研究拟通过临床-细胞-整体动物研究模式，探讨健脾清热活血方通过干预METTL3介导的m6A修饰抑制miR-196a-5p加工成熟，从而正向调控ACER2诱导的胃癌细胞保护性自噬，达到治疗胃癌的目的，阐明其部分作用机制为健脾清热活血方抑制胃癌发生发展提供实验依据，具有重要的临床意义。

The morbidity and mortality of gastric cancer(GC) occupied the second position in malignant tumors. Traditional Chinese medicine(TCM) takes certain advantages in the prevention and treatment of GC, however, the mechanism was not clearly demonstrated. Recent studies have found that N6-methyladenosine(m6A) dependent pri-miRNA processing modulating by METTL3 plays an important role in the occurrence and development of GC. Regulating the biological process of primary microRNA (pri-miRNA) processing into mature miRNA mediated by METTL3, may be a new idea to inhibit the occurrence and development of GC. The results of pre-experiment showed that Jianpi Qingre Huoxue formula (JQH) can inhibit the malignant behavior of GC cells, the ability of subcutaneous tumor formation in nude mice, and regulate the expression of METTL3 and miR-196a-5p. In this study, through the clinical-cell-whole animal model,we would explore the therapeutic effect of JQH on GC by interfering METTL3-mediated m6A modification, inhibiting the processing and maturation of pri-miR-196a into miR-196a-5p, which will positively regulate ACER2-induced protective autophagy in GC cells.By elucidating the partial mechanism of JQH, it will provide evidence-based support for it to prevent and cure GC, which has important clinical significance.