a National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences , Northwest University , Xi'an , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):725-736. doi: 10.1080/21691401.2019.1569530.
Oxaliplatin resistance limits the efficiency of treatment for colorectal cancer (CRC). Studies have shown that abnormal expression of microRNAs (miRNAs) were associated with tumorigenesis, cancer development and chemoresistance. The purpose of this study was to identify potential miRNAs related to oxaliplatin resistance in CRC cells. In this work, using small RNA sequencing (small RNA-Seq) and transcriptome sequencing (RNA-Seq), we found that down-regulated miR-483-3p was concurrent with up-regulated FAM171B in oxaliplatin-resistant colorectal cancer cell line HCT116/L as compared with its parental cell line HCT116. Transient transfection of miR-483-3p mimics markedly decreased the levels of FAM171B and restored oxaliplatin responsiveness of HCT116/L cells, and this alteration enhanced cell apoptosis and weakened cell migration. Whereas miR-483-3p inhibitor dramatically promoted the expression of FAM171B and enhanced oxaliplatin resistance of HCT116 cells by repressing cell apoptosis. Furthermore, knockdown of FAM171B in HCT116/L cells could also sensitize its reaction of the treatment with oxaliplatin, which was verified by the reduced cell migration. These findings demonstrate that FAM171B is a functional target of miR-483-3p in the regulation of oxaliplatin resistance in human CRC cells.
奥沙利铂耐药限制了结直肠癌（CRC）的治疗效率。研究表明，miRNAs（miRNAs）的异常表达与肿瘤发生、癌症发展和化疗耐药有关。本研究旨在鉴定与 CRC 细胞中奥沙利铂耐药相关的潜在 miRNAs。在这项工作中，我们使用小 RNA 测序（small RNA-Seq）和转录组测序（RNA-Seq），发现与亲本细胞系 HCT116 相比，奥沙利铂耐药的结直肠癌细胞系 HCT116/L 中下调的 miR-483-3p 与上调的 FAM171B 同时存在。瞬时转染 miR-483-3p 模拟物可显著降低 FAM171B 的水平并恢复 HCT116/L 细胞对奥沙利铂的敏感性，这种改变增强了细胞凋亡并减弱了细胞迁移。而 miR-483-3p 抑制剂通过抑制细胞凋亡显著促进 FAM171B 的表达并增强 HCT116 细胞对奥沙利铂的耐药性。此外，FAM171B 在 HCT116/L 细胞中的敲低也可以使其对奥沙利铂治疗的反应敏感，这通过减少细胞迁移得到了验证。这些发现表明 FAM171B 是 miR-483-3p 调节人 CRC 细胞奥沙利铂耐药的功能靶标。
