tRNA 衍生片段（tRFs）调控LncRNA MALAT-1影响结肠癌转移基因 SMC1A选择性剪接的机制分析

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA (lncRNA), which regulates alternative splicing by interaction with splicing factors. Structural maintenance of chromosomes 1A (SMC1A), a subunit of cohesin, could be alternatively spliced and products various transcripts with different functions. Recent studies indicated that the changes in tumor microenvironment, such as hypoxia, results in the differences in the expression of non-coding small RNA tRNA-derived fragments (tRFs), and subsequently affects the phenotype of tumor metastasis. Our previous studies revealed the significant correlation among the expression of tRFs, ELAC2, MALAT-1, SRSF and MALAT-1 through complete transcriptional sequencing and bioinformatics. Geen sequencing alignment indicated that tRFs could regulate the expression of MALAT-1 by binding to specific sites on MALAT-1. The aim of the present study, therefore, is to study the expression pattern and interaction between tRFs and MALAT-1，and further explore the mechanism of nocoding RNA in regulating alternative splicing. We explore the mechanism of tumor microenvironment in regulating alternative splicing of SMC1A through studying the interaction between different types of non-coding RNA, tend to reveal the influence of tumor microenvironment on tumor metastasis potential, and reach a in-depth understanding of the regulation mechanism of tumor metastasis from molecular initiation perspective.

Lnc RNA MALAT1通过影响剪切因子水平来调控选择性剪切。而SMC1A基因通过选择性剪切产生功能差异的不同转录本。tRFs是最近被重视的一类源于tRNA的非编码小RNA。肿瘤微环境的变化如缺氧等相关信号引起了tRFs的表达差异，且影响肿瘤转移表型。本课题组经过全转录本测序及生物信息学研究发现，低氧诱导的结肠癌细胞基因表达相关性分析提示tRFs，ELAC2，MALAT-1，SRSF，SMC1A存在显著表达相关性。基因序列比对分析预测发现关键tRF存在能够与MALAT-1结合的区域，影响MALAT-1的表达。本研究分析tRFs与MALAT-1的表达规律以及相互的作用关系，深入阐述非编码RNA调节选择性剪接过程的精细环节。从不同类型非编码RNA相互作用层面研究肿瘤微环境中SMC1A基因的选择性剪切机理，揭示肿瘤微环境对肿瘤转移潜能的影响，深层次理解肿瘤转移的分子始动调控机理。

Lnc RNA MALAT1通过影响剪切因子水平来调控选择性剪切。而SMC1A基因通过选择性剪切产生功能差异的不同转录本。tRFs是最近被重视的一类源于tRNA的非编码RNA。肿瘤微环境的变化如缺氧等相关信号引起了tRFs的表达差异，且影响肿瘤转移表型。本课题组经过全转录本测序及生物信息学研究发现，低氧诱导的结肠癌细胞基因表达相关性分析提示tRFs，ELAC2，MALAT-1，SRSF，SMC1A存在显著表达相关性。基因序列比对分析预测发现关键tRF存在能够与MALAT-1结合的区域，影响MALAT-1的表达。本研究分析tRFs与MALAT-1的表达规律以及相互的作用关系，深入阐述非编码RNA调节选择性剪接过程的精细环节。从不同类型非编码RNA相互作用层面研究肿瘤微环境中SMC1A基因的选择性剪切机理，揭示肿瘤微环境对肿瘤转移潜能的影响，深层次理解肿瘤转移的分子始动调控机理。