DIS3L2 promotes progression of hepatocellular carcinoma via hnRNP U-mediated alternative splicing

DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored.hnRNP U regulates the alternative splicing of pre-mRNA, and our results also showed that RNA promoted the interaction between DIS3L2 and hnRNP U, suggesting that DIS3L2 may be involved in splicing regulation. Thus, we next performed RNA-Seq to investigate whether DIS3L2 regulated pre-mRNA alternative splicing in cancer cells. Human hepatocellular carcinoma PLC cells were transfected with Dis3l2 shRNAs, hnRNP U shRNAs or non-targeting control shRNA followed by RNA extraction and sequenced on Illumina Novaseq (Homo sapiens).

类DIS3 3'-5'核糖核酸外切酶2（DIS3L2）可降解异常RNA，但其在肿瘤发生中的功能仍未得到充分研究。异质性核核糖核蛋白U（hnRNP U）能够调控前体mRNA（pre-mRNA）的可变剪接，本研究结果同时显示，RNA可促进DIS3L2与hnRNP U之间的相互作用，提示DIS3L2可能参与剪接调控过程。据此，本研究后续开展了RNA测序（RNA-Seq）实验，以探究DIS3L2是否可调控癌细胞中的前体mRNA可变剪接。将人肝癌PLC细胞转染Dis3l2短发夹RNA（shRNA）、hnRNP U短发夹RNA或非靶向对照短发夹RNA，随后提取RNA并在因美纳（Illumina）NovaSeq测序平台上完成测序（受试物种：智人）。