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  • Title: Mutations in GAS5 affect the transformation from benign prostate proliferation to aggressive prostate cancer by affecting the transcription efficiency of GAS5.
    Author: Zhu L, Zhu Q, Wen H, Huang X, Zheng G.
    Journal: J Cell Physiol; 2019 Jun; 234(6):8928-8940. PubMed ID: 30317620.
    Abstract:
    BACKGROUND: In this study, we aimed to explore the effects of GAS5 single-nucleotide polymorphisms (SNPs) on GAS5 expression. And the signaling pathways underlying the function of GAS5 during the pathogenesis of prostate cancer (PC) were clarified. MATERIALS AND METHODS: Patients with PC were recruited and grouped according to their specific genotypes of rs55829688 and rs145204276. Kaplan-Meier overall survival curves were calculated and compared among different groups. Real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry (IHC) assays were conducted to examine the expression of different factors involved in PC. And computational analyses and luciferase assays were conducted to clarify the regulatory relationships among the above factors. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to evaluate cell viability and apoptosis. RESULTS: The expression of GAS5, PDCD4, PTEN, and AKT was decreased gradually in the order of patient Group 1-4, whereas the expression of microRNA-21 (miR-21) and miR-1284 showed an opposite trend. GAS5 was identified to target miR-21 and miR-1284, whereas miR-21 and miR-1284 regulated the expression of PDCD4/PTEN and AKT, respectively. Moreover, the GAS5/miR-21/PDCD4/PTEN and GAS5/miR-1284/AKT signaling pathway was found to be closely related to the tumorigenesis of PC. CONCLUSIONS: GAS5 SNPs affected the survival rate and prognosis in patients with PC via regulating the expression of miR-21/miR-1284, which in turn affected the expression of PDCD4, PTEN, and AKT. GAS5 downregulated the expression of miR-21/miR-1284, thus leading to the elevated expression of key regulators of apoptosis. Therefore, the GAS5 SNPs may be used as key indicators for the diagnosis and prognosis prediction of PC.
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