Li Bai, Xie Zhongshi, Li Zhihong, Chen Si, Li Bo
Department of Colorectal and Anal Surgery, The First Hospital of Jilin University Changchun 130021, P. R. China.
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University Changchun 130033, P. R. China.
Am J Transl Res. 2016 Dec 15;8(12):5475-5484. eCollection 2016.
Increasing evidence indicates that dysregulation of miRNAs is involved in the initiation and progression of colorectal cancer (CRC). MicroRNA (miR)-613 has been reported to function as a tumor suppressor in many cancers. However, the precise role of miR-613 in CRC progression is unclear. This study aimed to investigate the role and underlying mechanism of miR-613 in growth and metastasis of CRC. Real-time quantitative PCR (qPCR) and western blot techniques were used to assess expression of miR-613 and formin-like 2 (FMNL2) in CRC cell lines and tissues. Luciferase reporter assays were conducted to investigate the association between miR-613 and FMNL2. Proliferation, wound healing, and transwell invasion assays, as well as flow cytometric analysis, were performed to evaluate the effect of miR-613 on proliferation, migration, invasion, and cell-cycle status, respectively, of CRC cells. We found that miR-613 was significantly downregulated in CRC cell lines and tissue samples, and correlated closely with TNM stage. miR-613 suppressed CRC cell proliferation, migration, and invasion, and induced cell-cycle arrest at G1 phase. FMNL2 was identified as a direct target of miR-613 in CRC cells. Importantly, FMNL2 overexpression rescued miR-613-induced suppression of proliferation, migration, and invasion of CRC cells. These results suggest that miR-613 functions as a tumor suppressor in the progression of CRC by regulating FMNL2.
越来越多的证据表明，微小RNA（miRNA）失调参与了结直肠癌（CRC）的发生和发展。据报道，微小RNA（miR）-613在许多癌症中发挥肿瘤抑制作用。然而，miR-613在CRC进展中的确切作用尚不清楚。本研究旨在探讨miR-613在CRC生长和转移中的作用及潜在机制。采用实时定量聚合酶链反应（qPCR）和蛋白质免疫印迹技术评估miR-613和formin样蛋白2（FMNL2）在CRC细胞系和组织中的表达。进行荧光素酶报告基因检测以研究miR-613与FMNL2之间的关联。分别进行增殖、伤口愈合、transwell侵袭实验以及流式细胞术分析，以评估miR-613对CRC细胞增殖、迁移、侵袭和细胞周期状态的影响。我们发现，miR-613在CRC细胞系和组织样本中显著下调，且与TNM分期密切相关。miR-613抑制CRC细胞的增殖、迁移和侵袭，并诱导细胞周期停滞在G1期。FMNL2被确定为CRC细胞中miR-613的直接靶点。重要的是，FMNL2过表达挽救了miR-613诱导的CRC细胞增殖、迁移和侵袭抑制。这些结果表明，miR-613通过调节FMNL2在CRC进展中发挥肿瘤抑制作用。
