piRNA-823通过调控线粒体自噬抑制结肠癌细胞凋亡的机制研究

piRNA是新发现的一类非编码小RNA并参与了多种癌症的发生发展。piRNA-823是申请者筛选出的在结肠癌中高表达且具有临床病理学意义的piRNA。预实验发现piRNA-823抑制剂促进结肠癌细胞线粒体自噬及凋亡。但piRNA-823、线粒体自噬及结肠癌细胞凋亡三者之间的关系及调控机制尚未明确。故首先分析piRNA-823在结肠癌组织和癌旁组织及结肠癌患者和健康志愿者外周血中的差异表达；其次通过过表达或沉默piRNA-823，在体内外实验中探讨piRNA-823对结肠癌细胞增殖、凋亡及线粒体自噬的影响；抑制线粒体自噬后，探讨piRNA-823是否通过调控线粒体自噬抑制结肠癌细胞的凋亡；最后利用分子生物学及表观遗传学研究方法明确piRNA-823调控线粒体自噬的机制。本研究对于发现结肠癌新的辅助诊断方法及开发以piRNA-823为靶点的治疗结肠癌药物具有重要意义。

piRNA is a newly identified small non-coding RNA and play an important role in cancer. piRNA-823 is the piRNA that were screened by the applicant and has the potential clinical application. The preliminary data indicated that piRNA-823 inhibitor promoted colon cancer cell mitophagy and apoptosis. However, the relationship and regulation mechanism among piRNA-823, mitophagy and apoptosis remained unclear. Therefore, the current study will first analyze the differential expression of piRNA-823 in the cancer and normal tissue. Next, after silencing or enhancing piRNA-823 expression, the effect of piRNA-823 on colon cancer cell proliferation, apoptosis and mitohagy will be investigated. By using mitophagy inhibitor, the applicants will clarify whether piRNA-823 modulates colon cancer cell apoptosis through mitohagy. Finally, molecular biology and epigenetic investigation approaches will be used to elucidate the regulation mechanism of piRNA-823 on mitophagy. This study will not only provide a new diagnosis method of CRC but also provides the potential target in treating the diseases.