A-to-I edited miR-154-p13-5p inhibited cell proliferation and migration and induced apoptosis by targeting LIX1L in the bladder cancer

A-to-I 编辑的 miR-154-p13-5p 通过靶向膀胱癌中的 LIX1L 抑制细胞增殖和迁移并诱导细胞凋亡

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作者:Zhengxiang Hu, Chunhui Liu, Zujun Mei, Xinlei Wang, Yuyang Ma, Xing Liu, Hao Xu, Gaochuan Fang, Xinyu Liu, Rui Li, Jie Wang, Zhenduo Shi, Conghui Han

Abstract

With the advancement of RNA sequencing technology, there has been a drive to uncover and elucidate the pivotal role of A-to-I RNA editing events in tumorigenesis. However, A-to-I miRNA editing events have been clearly identified in bladder cancer, the molecular mechanisms underlying their role in bladder cancer remain unclear. In our investigation, we observed a notable under-expression of edited miR-154-p13-5p in bladder cancer (BC) tissues, in contrast to normal counterparts. Remarkably, heightened expression levels of edited miR-154-p13-5p correlated with improved survival outcomes. To assess the impact of modified miR-154-p13-5p, we conducted a string of cell phenotype assays through transfection of the corresponding miRNAs or siRNAs. The results unequivocally demonstrate that edited miR-154-p13-5p exerts a substantial inhibitory influence on proliferation, migration, and induces apoptosis by specifically targeting LIX1L in bladder cancer. Moreover, we observed that the editing of miR-154-p13-5p or LIX1L-siRNAs inhibits the expression of LIX1L, thereby suppressing EMT-related proteins and cell cycle protein CDK2. Simultaneously, an upregulation in the expression levels of Caspase-3 and Cleaved Caspase-3 were also detected. Our research findings suggest that the upregulation of edited miR-154-p13-5p could potentially enhance the prognosis of bladder cancer, thereby presenting molecular biology-based therapeutic strategies.

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