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

Lu,Zhan-Jun; Lu,Lun-Gen; Tao,Kai-Zhong; Chen,Da-Fan; Xia,Qing; Weng,Jian‑Jun; Zhu,Feng; Wang,Xing-Peng; Zheng,Ping

doi:10.3892/mmr.2014.2562

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

Authors:
- Zhan-Jun Lu
- Lun-Gen Lu
- Kai-Zhong Tao
- Da-Fan Chen
- Qing Xia
- Jian‑Jun Weng
- Feng Zhu
- Xing-Peng Wang
- Ping Zheng
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Affiliations: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China, Department of Gastroenterology, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China
Published online on: September 12, 2014 https://doi.org/10.3892/mmr.2014.2562
Pages: 2401-2408

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Abstract

MicroRNAs (miRs) are small non‑coding 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 miR‑185 in the development of human colon cancer has not yet been investigated. In this study, the association between miR‑185 expression and the clinicopathological characteristics of patients with colon cancer was analyzed using quantitative polymerase chain reaction (qPCR). Using a gain‑of‑function approach, the effects of miR‑185 overexpression on the expression of hypoxia‑inducible factor‑2α (HIF‑2α), proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase‑2 (MMP‑2) 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 miR‑185. miR‑185 was found to be significantly downregulated in cancer tissues compared with adjacent non‑cancerous tissues, and was negatively correlated with lymph node metastasis of colon cancer (P<0.001). miR‑185 overexpression in vitro impeded cellular proliferation and invasive potential with reduced expression of HIF‑2α, PCNA and MMP‑2 in SW620 cells transfected with an miR‑185 mimic. In addition, the tumor volumes in SW620 subcutaneous nude mouse models treated with miR‑185 were significantly smaller than those of the control group. In conclusion, these findings indicate that miR‑185 as a tumor suppressor may affect the development of colon cancer cells via inhibition of HIF‑2α signaling, suggesting that miR‑185 may serve as a potential therapeutic target in cancer treatment.

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