Zhu Wei, Long Jia-Li, Yin Yu-Ting, Guo Hai-Na, Jiang En-Ping, Li Yu-Ling, He Qing-Lian, Zeng Chao, Sun Yan-Qin
Department of Pathology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
Department of Pathology, Dongguan Maternal and Child Health Hospital, Dongguan, Guangdong 523002, P.R. China.
Exp Ther Med. 2019 Oct;18(4):2459-2466. doi: 10.3892/etm.2019.7826. Epub 2019 Jul 30.
MicroRNAs (miRNAs/miRs) are small non-coding RNAs that serve a post-transcriptional regulatory role in eukaryotes. Previous studies have demonstrated that the expression of miR-34a in colorectal cancer (CRC) tissues is decreased compared with that in normal colorectal tissues. However, the role of miR-34a in the invasion and metastasis of CRC remains unclear. In the present study, the levels of miR-34a expression were measured in various CRC cell lines. The cells were transfected with miR-34a mimics or inhibitors in order to assess the proliferation rate, and the colony forming, invasive and migratory abilities. Furthermore, the protein expression levels of vimentin and early growth response protein 1 (EGR1) were examined by western blot analysis. The results revealed that the expression of miR-34a was low in SW620, RKO, LoVo and Caco-2 cell lines and high in the SW480 and SW1116 cell lines. The migration, invasion and proliferation levels of SW480 cells were facilitated by decreasing the expression of miR-34a. Transient transfection with miR-34a mimics in SW620 cells caused a notable decrease in cell migration, invasion and proliferation levels compared with the control group, and a downregulation of vimentin and upregulation of EGR1 protein expression. The present study demonstrated that miR-34a was deregulated in a highly invasive CRC cell lines, and that it may attenuate the migratory, invasive and proliferative capabilities of CRC cells by enhancing the expression of EGR1 and inhibiting that of vimentin. The results of the present study represent important progress towards understanding the mechanisms of CRC recurrence and metastasis.
微小RNA(miRNA/miR)是一类小的非编码RNA,在真核生物中发挥转录后调控作用。先前的研究表明,与正常结直肠组织相比,结直肠癌(CRC)组织中miR-34a的表达降低。然而,miR-34a在CRC侵袭和转移中的作用仍不清楚。在本研究中,检测了各种CRC细胞系中miR-34a的表达水平。为了评估增殖率、集落形成能力、侵袭和迁移能力,用miR-34a模拟物或抑制剂转染细胞。此外,通过蛋白质印迹分析检测波形蛋白和早期生长反应蛋白1(EGR1)的蛋白质表达水平。结果显示,miR-34a在SW620、RKO、LoVo和Caco-2细胞系中表达较低,在SW480和SW1116细胞系中表达较高。降低miR-34a的表达促进了SW480细胞的迁移、侵袭和增殖水平。与对照组相比,用miR-34a模拟物瞬时转染SW620细胞导致细胞迁移、侵袭和增殖水平显著降低,波形蛋白下调,EGR1蛋白表达上调。本研究表明,miR-34a在高侵袭性CRC细胞系中表达失调,并且它可能通过增强EGR1的表达和抑制波形蛋白的表达来减弱CRC细胞的迁移、侵袭和增殖能力。本研究结果代表了在理解CRC复发和转移机制方面的重要进展。