MicroRNA-185 suppresses growth and invasion of colon cancer cells through inhibition of the hypoxiainducible factor-2α pathway in vitro and in vivo

Abstract

MicroRNAs (miRs) are small noncoding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer development and progression. However, the function of miR185 in the development of human colon cancer has not yet been investigated. In this study, the association between miR185 expression and the clinicopathological characteristics of patients with colon cancer was analyzed using quantitative polymerase chain reaction (qPCR). Using a gainoffunction approach, the effects of miR185 overexpression on the expression of hypoxiainducible factor2α (HIF2α), proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase2 (MMP2) were investigated in SW620 colon cancer cells using qPCR and western blotting. Functional analysis of cellular proliferative activities, by MTT assay, and invasive potential, by Transwell assay, was conducted on SW620 cells expressing low levels of miR185. miR185 was found to be significantly downregulated in cancer tissues compared with adjacent noncancerous tissues, and was negatively correlated with lymph node metastasis of colon cancer (P<0.001). miR185 overexpression in vitro impeded cellular proliferation and invasive potential with reduced expression of HIF2α, PCNA and MMP2 in SW620 cells transfected with an miR185 mimic. In addition, the tumor volumes in SW620 subcutaneous nude mouse models treated with miR185 were significantly smaller than those of the control group. In conclusion, these findings indicate that miR185 as a tumor suppressor may affect the development of colon cancer cells via inhibition of HIF2α signaling, suggesting that miR185 may serve as a potential therapeutic target in cancer treatment.