Section for Surgery, Department of Clinical Sciences, Skåne University Hospital, Lund University, 20502, Malmö, Sweden.
Sci Rep. 2020 Oct 9;10(1):16934. doi: 10.1038/s41598-020-73792-9.
Colon cancer is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the most insidious aspect of cancer progression. Convincing data suggest that microRNAs (miRs) play a key function in colon cancer biology. We examined the role of miR-340-5p in regulating RhoA expression as well as cell migration and invasion in colon cancer cells. Levels of miR-340-5p and RhoA mRNA varied inversely in serum-free and serum-grown HT-29 and AZ-97 colon cancer cells. It was found transfection with miR-340-5p not only decreased expression of RhoA mRNA and protein levels in HT-29 cells but also reduced colon cancer cell migration and invasion. Bioinformatics analysis predicted one putative binding sites at the 3'-UTR of RhoA mRNA. Targeting this binding site with a specific blocker reversed mimic miR-340-5p-induced inhibition of RhoA activation and colon cancer cell migration and invasion. These novel results suggest that miR-340-5p is an important regulator of colon cancer cell motility via targeting of RhoA and further experiments are warranted to evaluate the role of miR-340-5p in colon cancer metastasis.
结肠癌是全球第三大常见癌症,也是癌症相关死亡的重要原因。转移是癌症进展最阴险的方面。令人信服的证据表明,微小 RNA(miRs)在结肠癌生物学中起着关键作用。我们研究了 miR-340-5p 在调节 RhoA 表达以及结肠癌细胞迁移和侵袭中的作用。在无血清和血清培养的 HT-29 和 AZ-97 结肠癌细胞中,miR-340-5p 的水平与 RhoA mRNA 呈负相关。研究发现,miR-340-5p 的转染不仅降低了 HT-29 细胞中 RhoA mRNA 和蛋白水平的表达,还降低了结肠癌细胞的迁移和侵袭。生物信息学分析预测 RhoA mRNA 3'-UTR 上有一个潜在的结合位点。用特异性阻断剂靶向该结合位点可逆转模拟 miR-340-5p 诱导的 RhoA 激活和结肠癌细胞迁移和侵袭的抑制作用。这些新发现表明,miR-340-5p 通过靶向 RhoA 是结肠癌细胞运动的重要调节因子,需要进一步的实验来评估 miR-340-5p 在结肠癌转移中的作用。