Wang Kai-Yu, Ma Jun, Zhang Fu-Xi, Yu Ming-Jun, Xue Ji-Shan, Zhao Ji-Sheng
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China; Department of General Surgery, Affiliated Hospital of Beihua University, Jilin, China.
IUBMB Life. 2014 Sep;66(9):645-54. doi: 10.1002/iub.1317.
MicroRNAs (miRNAs) are small noncoding RNAs that participate in a variety of biological processes, and dysregulation of miRNAs is widely associated with cancer development and progression. MiR-378 is frequently downregulated in colorectal cancer (CRC) and colorectal cell lines; however, it has high serum levels. Bioinformatics analysis further deduced that CDC40 is a potential target of miR-378, and luciferase reporter assays confirmed the direct regulation of CDC40 by miR-378. CDC40 plays a key role in cell cycle progression through G1/S and G2/M and pre-mRNA splicing. Subsequently, we determined that miR-378 inhibits cell growth and the G1/S transition in CRC cells and that these effects were CDC40-dependent. Finally, miR-378 increased cell apoptosis induced by the chemotherapeutic drug L-OHP. Our data highlight the potential application of miR-378 as a tumor suppressor for CRC therapy and overcoming chemoresistance, and it may also be a potential tumor marker for CRC prognosis.
微小RNA（miRNA）是参与多种生物学过程的小型非编码RNA，miRNA的失调与癌症的发生和发展广泛相关。MiR-378在结直肠癌（CRC）和结直肠癌细胞系中经常下调；然而，它在血清中的水平较高。生物信息学分析进一步推断，细胞分裂周期蛋白40（CDC40）是miR-378的潜在靶标，荧光素酶报告基因检测证实了miR-378对CDC40的直接调控。CDC40在细胞通过G1/S和G2/M期的细胞周期进程以及前体mRNA剪接中起关键作用。随后，我们确定miR-378抑制CRC细胞的生长和G1/S期转换，并且这些作用依赖于CDC40。最后，miR-378增加了化疗药物奥沙利铂（L-OHP）诱导的细胞凋亡。我们的数据突出了miR-378作为CRC治疗的肿瘤抑制因子以及克服化疗耐药性的潜在应用，它也可能是CRC预后的潜在肿瘤标志物。
