miR-205通过靶向MDM4抑制结肠癌细胞迁移、侵袭和上皮间充质转化

Abstract

Colon cancer is one of the most frequent malignant tumors, and microRNA (miR)‑205 is involved in the tumor progression. The present study aimed to explore the effects of miR‑205 on human colon cancer and its targeting mechanism. The levels of miR‑205 and mouse double minute 4 (MDM4) were determined via reverse transcription‑quantitative (RT‑q)PCR and western blot analysis. A luciferase activity assay was performed to analyze the association between miR‑205 and MDM4. Cell viability, migration and invasion were determined via Cell Counting Kit‑8, wound healing and Transwell assays, respectively. The levels of epithelial‑mesenchymal transition (EMT)‑associated factors were determined by RT‑qPCR and western blot analysis. It was identified that MDM4 was overexpressed in colon cancer tissues and cells, and that there was a negative correlation between miR‑205 and MDM4 expression in colon cancer. Similarly, miR‑205 inhibited MDM4 expression by binding to its 3'untranslated region. in addition, miR‑205 directly targeted MDM4, accompanied by suppressed proliferation, migration and invasion of HCT116 cells. EMT processes were suppressed in miR‑205‑overexpressed cells; upregulation of E‑cadherin, and downregulation of N‑cadherin, vimentin, matrix metalloproteinase (MMP)2 and MMP9 were observed. Collectively, miR‑205 conspicuously depressed the viability, migration, invasion and EMT process of human colon cancer cells via targeting MDM4. miR‑205 could be potentially used in the treatment of human colon cancer.