长链非编码RNA介导miRNA的成熟对舌鳞癌细胞线粒体分裂和顺铂化疗敏感性的调控作用

申请人近年以线粒体分裂作为切入点，首次发现线粒体分裂可调控舌鳞癌顺铂化疗敏感性，其中miRNA是重要的调控轴心分子。最新研究发现长链非编码RNA（lncRNA）可介导miRNA的成熟，那么lncRNA是否可通过调控miRNA的成熟进而影响舌鳞癌线粒体分裂和顺铂化疗敏感性呢？我们预实验初步发现lncRNA NR_029377可调控pre-miR-483剪切生成成熟的miR-483。因而本课题将基于lncRNA芯片筛选调控舌鳞癌线粒体分裂和顺铂化疗敏感性的功能lncRNA，对lncRNA干预后以miRNA芯片筛选其调控的下游关键miRNA，验明lncRNA-miRNA以及miRNA子通路对舌鳞癌细胞线粒体分裂和顺铂化疗敏感性的作用，机制研究聚焦于lncRNA介导miRNA前体结构在胞核和胞质中的剪切过程，从而全面剖析lncRNA对miRNA成熟的调控机制，为研究顺铂化疗敏感性提供新思路。

Starting with the mitochondrial fission, the applicant has first revealed the regulatory role of mitochondrial fission in the cisplatin sensitivity of tongue squamous cell carcinoma, involving miRNAs as an important regulatory axis molecule, in recent years. The latest study demonstrating that long non-coding RNAs (lncRNAs) can mediate the mature process of miRNAs, raises the question that whether lncRNAs can affect the mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma via regulating miRNAs maturation. Given that our preliminary experiments have detected the regulatory function of lncRNA NR_029377 on the pre-miR-483 splicing to mature miR-483, we will screen the lncRNAs basing on regulation of the mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by using lncRNA array in the present study. Then, to verify the biological functions of lncRNA-miRNA and miRNAs pathway, we will select key miRNAs by miRNA microarray following lncRNAs knockdown. And we will focus on the splicing process of pri(pre)-miRNAs mediated by lncRNAs in the nucleus and cytoplasm, thereby getting a comprehensive investigation of regulatory mechanism of lncRNAs on miRNAs maturation and providing a novel idea for the study on cisplatin sensitivity.