Department of Ultrasonic Diagnosis, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Department of Orthopedic Surgery, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang, People's Republic of China.
Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G827-G839. doi: 10.1152/ajpgi.00369.2019. Epub 2020 Mar 16.
There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524-5p has been reported to possess anticancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of the miRNA-524-5p/with-no-lysine kinase 1 (WNK1) system on angiogenesis in a colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. We found miRNA-524-5p expression was relatively high in COLO205 cells and relatively low in HT-29 cells. Elevating miRNA-524-5p expression inhibited proliferation, induced cycle arrest, diminished vascular endothelial growth factor production, and thereby suppressed angiogenesis in HT-29 cells. WNK1 silencing exerted the ability of antiangiogenesis in HT-29 cells. Besides, miRNA-524-5p deficiency-induced angiogenesis was impeded by WNK1 silence in COLO205 cells. In a murine tumor model, miRNA-524-5p agomir treatment significantly suppressed colon cancer tumorigenicity with the downregulation of WNK1 expression. In summary, our results indicated that miRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting WNK1. MiRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting with-no-lysine kinase 1.
越来越多的证据表明,miRNA(miRNA)异常参与了各种恶性肿瘤的发生和发展,包括结肠癌。有报道称 miRNA-524-5p 在各种肿瘤中具有抗癌活性,但在结肠癌细胞中很少研究其功能。本研究旨在探讨 miRNA-524-5p/无赖氨酸激酶 1(WNK1)系统对结肠癌细胞系(HT-29 和 COLO205 细胞)血管生成的影响,并进一步探讨其潜在机制。我们发现 miRNA-524-5p 在 COLO205 细胞中的表达相对较高,而在 HT-29 细胞中的表达相对较低。上调 miRNA-524-5p 的表达抑制了 HT-29 细胞的增殖,诱导了细胞周期停滞,减少了血管内皮生长因子的产生,从而抑制了血管生成。WNK1 沉默在 HT-29 细胞中发挥了抗血管生成的作用。此外,在 COLO205 细胞中,miRNA-524-5p 缺乏诱导的血管生成被 WNK1 沉默所抑制。在小鼠肿瘤模型中,miRNA-524-5p 激动剂治疗显著抑制了结肠癌的致瘤性,同时下调了 WNK1 的表达。总之,我们的研究结果表明,miRNA-524-5p 通过靶向 WNK1 抑制结肠癌细胞的血管生成。miRNA-524-5p 通过靶向无赖氨酸激酶 1 抑制结肠癌细胞的血管生成。