Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Department of Oncology, Jingjiang People's Hospital, Jingjiang, Jiangsu 214504, China.
Biomed Res Int. 2021 Apr 28;2021:9951405. doi: 10.1155/2021/9951405. eCollection 2021.
Although colorectal cancer (CRC) is common, there is a paucity of information regarding its molecular pathogenesis. Studies have shown that miRNAs play pivotal roles in the development and progression of CRC. There is a need to further investigate the biological functions of miRNAs in CRC. In particular, it has been reported that miR-942-5p exhibits tumor-suppressive properties. Thus, we analyzed the functional significance of miR-942-5p in CRC and the underlying molecular mechanisms. We found that miR-942-5p was downregulated in CRC tissues and cells. Cell Counting Kit-8, EdU, and colony formation assays revealed that the overexpression of miR-942-5p by mimics inhibited the proliferation of CRC cells. Use of the miR-942-5p inhibitor effectively enhanced the proliferative potential of CRC cells. Further, xenograft experiments confirmed these results. Increased expression of miR-942-5p suppressed the invasion, migration, and epithelial-mesenchymal transition of CRC cell lines, while decreased miR-942-5p expression had the opposite effect. CCBE1, a secretory molecule for lymphangiogenesis, was established as a downstream target of miR-942-5p, and its expression was inversely correlated with the expression of miR-942-5p in CRC cells. Additionally, cotransfection of the miR-942-5p inhibitor with si-CCBE1 into CRC cells reversed the effects induced by miR-942-5p overexpression. In conclusion, we confirmed that miR-942-5p exerts oncogenic actions in CRC by targeting CCBE1 and identified miR-942-5p as a potential clinical biomarker for CRC diagnosis and therapy.
尽管结直肠癌(CRC)很常见,但关于其分子发病机制的信息却很少。研究表明,miRNAs 在 CRC 的发生和发展中起着关键作用。需要进一步研究 miRNAs 在 CRC 中的生物学功能。特别是,据报道 miR-942-5p 具有肿瘤抑制特性。因此,我们分析了 miR-942-5p 在 CRC 中的功能意义及其潜在的分子机制。我们发现 miR-942-5p 在 CRC 组织和细胞中下调。细胞计数试剂盒-8、EdU 和集落形成实验表明,miR-942-5p 模拟物的过表达抑制了 CRC 细胞的增殖。使用 miR-942-5p 抑制剂有效地增强了 CRC 细胞的增殖潜能。此外,异种移植实验证实了这些结果。miR-942-5p 的表达增加抑制了 CRC 细胞系的侵袭、迁移和上皮间质转化,而 miR-942-5p 表达的减少则产生相反的效果。CCBE1 是淋巴管生成的分泌分子,被确定为 miR-942-5p 的下游靶标,其在 CRC 细胞中的表达与 miR-942-5p 的表达呈负相关。此外,将 miR-942-5p 抑制剂与 si-CCBE1 共转染到 CRC 细胞中,逆转了 miR-942-5p 过表达引起的作用。总之,我们证实 miR-942-5p 通过靶向 CCBE1 在 CRC 中发挥致癌作用,并将 miR-942-5p 鉴定为 CRC 诊断和治疗的潜在临床生物标志物。