title: MicroRNA-185 suppresses growth and invasion of colon cancer cells through inhibition of the hypoxia‑inducible factor-2α pathway in vitro and in vivo.
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.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Zhan-Jun
authors.initials: ZJ
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Lun-Gen
authors.initials: LG
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Kai-Zhong
authors.initials: KZ
authors.lastname: Tao
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Da-Fan
authors.initials: DF
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Weng
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D019073:HT29 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D015398:Signal Transduction; D047368:Tumor Burden; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D000099162:Endothelial PAS Domain-Containing Protein 1; C552431:MIRN185 microRNA, human