microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway

European Journal of Histochemistry

XuanXu¹  XiaolinPan¹  YangHu¹  GuilianLan¹  JiaoyuAi¹  XinHuang¹  HuajingKe¹  Yao Wu¹  RuyiXie² 

[1] Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Gastroenterology, Nanchang;Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Gastroenterology, Nanchang;

关键词: miR-16-5p;    FOXK1;    PI3K/Akt/mTOR;    Colorectal cancer;    Proliferation;    Angiogenesis;   

DOI  :  10.4081/ejh.2022.3333

来源: DOAJ

【 摘 要 】

MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.

【 授权许可】

Unknown