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MiR-199a regulates cell proliferation and survival by targeting FZD7.

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机构: [1]Department of Gastroenterology, the 309th Hospital of Chinese People’s Liberation Army, Beijing, PR China [2]State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, PR China [3]Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, PR China [4]Department of XiShan Outpatient Clinic, the 309th Hospital of Chinese People’s Liberation Army, Beijing, PR China [5]Department of Digestion, General Hospital of Chengdu Military Command, Chengdu, Sichuan Province, PR China [6]Department of Medical, the 309th Hospital of Chinese People’s Liberation Army, Beijing, PR China, [7]Asian Games Village Clinic of Logistics Department, the General Armament Department of PLA, Beijing, PR China [8]Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, PR China
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摘要:
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.

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出版当年[2014]版:
大类 | 3 区 生物
小类 | 3 区 综合性期刊
最新[2023]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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第一作者机构: [1]Department of Gastroenterology, the 309th Hospital of Chinese People’s Liberation Army, Beijing, PR China [2]State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, PR China
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