Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
Sci Rep. 2019 Nov 1;9(1):15803. doi: 10.1038/s41598-019-52225-2.
Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Liver metastasis is the major cause of CRC patient mortality, occurring in 60% patients with no effective therapies. Although studies have indicated the role of miRNAs in CRC, an in-depth miRNA expression analysis is essential to identify clinically relevant miRNAs and understand their potential in targeting liver metastasis. Here we analyzed miRNA expressions in 405 patient tumors from publicly available colorectal cancer genome sequencing project database. Our analyses showed miR-132, miR-378f, miR-605 and miR-1976 to be the most significantly downregulated miRNAs in primary and CRC liver metastatic tissues, and CRC cell lines. Observations in CRC cell lines indicated that ectopic expressions of miR-378f, -605 and -1976 suppress CRC cell proliferation, anchorage independent growth, metastatic potential, and enhance apoptosis. Consistently, CRC patients with higher miR-378f and miR-1976 levels exhibited better survival. Together, our data suggests an anti-tumorigenic role of these miRNAs in CRC and warrant future in vivo evaluation of the molecules for developing biomarkers or novel therapeutic strategies.
结直肠癌（CRC）是全球癌症相关死亡的第四大主要原因。肝转移是 CRC 患者死亡的主要原因，在无有效治疗方法的患者中，60%发生肝转移。尽管研究表明 miRNA 在 CRC 中的作用，但深入的 miRNA 表达分析对于确定临床相关的 miRNA 并了解其在靶向肝转移中的潜力至关重要。在这里，我们分析了来自公开的结直肠癌基因组测序项目数据库的 405 名患者肿瘤中的 miRNA 表达。我们的分析表明，miR-132、miR-378f、miR-605 和 miR-1976 是原发性和 CRC 肝转移组织以及 CRC 细胞系中下调最显著的 miRNA。在 CRC 细胞系中的观察结果表明，miR-378f、-605 和 -1976 的异位表达可抑制 CRC 细胞的增殖、锚定非依赖性生长、转移潜能，并增强细胞凋亡。一致地，miR-378f 和 miR-1976 水平较高的 CRC 患者的生存情况更好。总之，我们的数据表明这些 miRNA 在 CRC 中具有抗肿瘤作用，需要进一步在体内评估这些分子，以开发生物标志物或新的治疗策略。
