tRF-20-M0NK5Y93-induced MALAT1 promotes colon cancer metastasis through alternative splicing of SMC1A.

Recent studies have indicated that changes in the tumor microenvironment, such as hypoxia, result in the discrepant expression of noncoding small RNA tRNA-derived fragments (tRFs), affecting the phenotype of tumor metastasis. The biological function of tRFs in tumors has attracted increasing attention, but the mechanism by which tRFs mediate tumor metastasis has not been clarified. The direct regulatory relationship between tRFs and lncRNAs and the mechanism by which noncoding RNAs regulate alternative splicing are still unknown. In this study, the mechanism of tRF-mediated SMC1A alternative splicing and regulation of colon cancer metastasis was studied from multiple dimensions of cell, molecule, animal and clinical. Our present studies revealed that tRF-20-M0NK5Y93 inhibits colon cancer metastasis and that there is a significant correlation between the expression of tRFs, metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), and SRSF2 through complete transcriptional sequencing and bioinformatics. Mechanistic investigations indicated that tRFs could regulate the expression of MALAT-1 by binding to specific sites on MALAT-1. MALAT1, which is a long noncoding RNA (lncRNA), regulates alternative splicing of (structural maintenance of chromosomes 1A) SMC1A by interaction with SRSF2, resulting in discrepant expression of various isoforms, SMC1A001, SMC1A201, SMC1A005, and SMC1A003. Our findings revealed the interaction between different types of noncoding RNAs on alternative splicing, which is expected to be a novel potential therapeutic target.