tRNA衍生片段tRF-Ser-TGA-008调控PREX1表达抑制皮肤黑素瘤侵袭转移的作用及机制研究

皮肤黑色素瘤（Cutaneous melanoma，CM）是恶性程度最高的皮肤肿瘤，病死率高、预后差。侵袭转移是造成死亡及影响预后的主要因素。tRFs（tRNA derived fragments）是最新鉴定的非编码RNA调控分子，可参与多种生理病理过程的调节。目前，tRFs与CM发生发展的关系尚未知。我们前期发现tRF-Ser-TGA-008可参与CM细胞迁移侵袭及EMT调节，并以类miRNA作用方式抑制PREX1基因表达。PREX1可调节发育时黑素细胞迁移，并在CM发生和侵袭转移中扮演重要癌基因作用。基于此，我们推测tRF-Ser-TGA-008通过靶向抑制PREX1表达抑制CM细胞侵袭转移。本研究拟通过多种生物学技术手段，探讨tRF-Ser-TGA-008调控CM细胞侵袭转移的作用及具体分子机制，为转移性CM诊疗分子靶标的寻找及研发提供思路和依据，具有重要的理论及临床参考意义。

Cutaneous melanoma (CM) is the most aggressive skin cancer characterized with high mortality . Invasion and metastasis are the main reasons that lead to death.tRNA-derived -fragments( tRFs ) are newly identified non-coding RNA molecules that participate in the regulation of various physiological and pathological processes .Up to date,there is no report on the participation of tRFs in CM invasion and metastasis .Our previous studies found tRF-Ser-TGA-008 inhibited migration and invasion of CM cells via regulating EMT. Mechanistically, tRF-Ser-TGA-008 decreased PREX1 expression in miRNA-like mechanism. PREX1 is well known to regulate normal melanocyte migration during early development and also positively related to the occurrence and development of CM. Based on these, we speculate tRF-Ser-TGA-008 inhibits migration and invasion of CM cells by inhibition of PREX1 expression.Our study intends to explore the role and mechanism of tRF-Ser-TGA-008 in migration and invasion of CM cells through various molecular and cellular biological techniques. This will povided evidence and theoretical basis for future diagnosis and treatment for metastatic cutaneous melanoma.