title: MiR-199a regulates cell proliferation and survival by targeting FZD7.
abstract: A growing amount of evidence indicates that miRNAs are important regulators of multiple cellular processes and, when expressed aberrantly in different types of cancer such as hepatocellular carcinoma (HCC), play significant roles in tumorigenesis and progression. Aberrant expression of miR-199a-5p (also called miR-199a) was found to contribute to carcinogenesis in different types of cancer, including HCC. However, the precise molecular mechanism is not yet fully understood. The present study showed that miR-199a is frequently down-regulated in HCC tissues and cells. Importantly, lower expression of miR-199a was significantly correlated with the malignant potential and poor prognosis of HCC, and restoration of miR-199a in HCC cells led to inhibition of the cell proliferation and cell cycle in vitro and in vivo. Furthermore, Frizzled type 7 receptor (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-199a. In addition, these findings were further strengthened by results showing that expression of FZD7 was inversely correlated with miR-199a in both HCC tissues and cells and that over-expression of miR-199a could significantly down-regulate the expression of genes downstream of FZD7, including β-catenin, Jun, Cyclin D1 and Myc. In conclusion, these findings not only help us to better elucidate the molecular mechanisms of hepatocarcinogenesis from a fresh perspective but also provide a new theoretical basis to further investigate miR-199a as a potential biomarker and a promising approach for HCC treatment.
authors.affiliation: Department of Gastroenterology, the 309th Hospital of Chinese People's Liberation Army, Beijing, PR China; State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jiugang
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors.forename: Liucun
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of XiShan Outpatient Clinic, the 309th Hospital of Chinese People's Liberation Army, Beijing, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China; Department of Digestion, General Hospital of Chengdu Military Command, Chengdu, Sichuan Province, PR China.
authors.forename: Shanhong
authors.initials: S
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Huahong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Medical, the 309th Hospital of Chinese People's Liberation Army, Beijing, PR China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Asian Games Village Clinic of Logistics Department, the General Armament Department of PLA, Beijing, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Gou
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D034622:RNA Interference
chemical_list: C115810:FZD7 protein, human; D051157:Frizzled Receptors; D035683:MicroRNAs; C531408:mirn199 microRNA, human