Dataset Information

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.

ABSTRACT: UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K₂ and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. In addition, GGPP was required to maintain the function of UBIAD1 in regulating the Ras/ERK signaling pathway. A Drosophila model was employed to confirm the function of UBIAD1/HEIX in vivo. The activation of Ras/ERK signaling at the plasma membrane induced melanotic masses in Drosophila larvae. Our study suggests that UBIAD1 serves as a tumor suppressor in cancer and tentatively reveals the underlying mechanism of melanotic mass formation in Drosophila.

SUBMITTER: Xu Z

PROVIDER: S-EPMC6281600 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.

Xu Zhiliang Z Duan Fengsen F Lu Huiai H Abdulkadhim Dragh Maytham M Xia Yanzhi Y Liang Huageng H Hong Ling L

Cell death & disease 20181205 12

UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K<sub>2</sub> and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the pro ...[more]

PMID: 30518913

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Project description:The purpose of our study is to elucidate the expression of lncRNA00518 (lnc00518) in the bladder cancer, and its potential mechanism in regulating the development of bladder cancer. The expression of lnc00518 in bladder cancer tissues and cells was examined by qRT-PCR. Correlation between lnc00518 expression with clinicopathologic characteristics and prognosis of bladder cancer patients was analyzed. In vitro effects of lnc00518 on the cellular behaviors of bladder cancer cells were explored. Moreover, in vivo effect of lnc00518 was evaluated by subcutaneous tumorigenesis in nude mice. The possible miRNA targets of lnc00518 were predicted by bioinformatics and further confirmed by dual-luciferase reporter gene assay, RIP and rescue experiments. Lnc00518 was highly expressed in bladder cancer tissues and cells. Lnc00518 expression was correlated with TNM staging and histological grade of bladder cancer. Besides, the overall survival was lower in bladder cancer patients with high expression of lnc00518 relative to those with low expression. Overexpression of lnc00518 enhanced proliferative, invasive, migratory potentials and clonality, but shortened G0/G1 phase of bladder cancer cells. Lnc00518 knockdown obtained the opposite trends. In vivo experiments revealed that lnc00518 knockdown inhibited subcutaneous tumorigenesis in nude mice. QRT-PCR results indicated that lnc00518 expression was negatively correlated with miRNA-101 expression in bladder cancer cells. Through dual-luciferase reporter gene assay and RIP, we confirmed the binding between lnc00518 and miRNA-101. Furthermore, EZH2 was verified to be the target of miRNA-101. MiRNA-101 knockdown reversed the inhibitory roles of lnc00518 knockdown in proliferative, migratory and invasive potentials of bladder cancer cells. Lnc00518 is highly expressed in bladder cancer and can be served as a predictor of poor prognosis. Lnc00518 promotes the proliferative, invasive and migratory potentials of bladder cancer by upregulating EZH2 via competitively binding to miRNA-101.

Dataset Information

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.

Publications

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras.

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