Dataset Information

Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/?-catenin signal pathway in hepatocellular carcinoma.

ABSTRACT: Previous evidences reveal that long non-coding RNA (lncRNA) down syndrome critical region 8 (DSCR8) involves in the progression of multiple cancers. However, the exact expression, function, and mechanism of DSCR8 in hepatocellular carcinoma (HCC) remain uncovered. In this study, real-time PCR in HCC tissues and cell lines indicated that DSCR8 expression was upregulated, while miR-485-5p was downregulated. MTT assay, plate clone formation, Edu assay, flow cytometry, and in vivo experiments indicated that DSCR8 promoted HCC cell proliferation and cycle, whereas accelerated cell apoptosis. Luciferase reporter gene assay, RIP assay, and rescue experiments demonstrated that DSCR8 functioned as a competing endogenous RNA (ceRNA) by sponging miR-485-5p in HCC cells. Furthermore, gain- and loss-of-function studies showed that miR-485-5p activated Wnt/?-catenin signal pathway by targeting Frizzled-7 (FZD7). Moreover, DSCR8 activated Wnt/?-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. Statistical analysis revealed that DSCR8 and miR-485-5p were closely related to some malignant clinicopathological features and 5-year survival rates of HCC patients. Taken together, the present study reports for the first time that DSCR8 activates Wnt/?-catenin signal pathway to promote HCC progression by DSCR8/miR-485-5p/FZD7 axis. The findings provide promising and valuable strategies for targeted therapy of HCC.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6113322 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma.

Wang Yufeng Y Sun Liankang L Wang Liang L Liu Zhikui Z Li Qing Q Yao Bowen B Wang Cong C Chen Tianxiang T Tu Kangsheng K Liu Qingguang Q

Cell death & disease 20180828 9

Previous evidences reveal that long non-coding RNA (lncRNA) down syndrome critical region 8 (DSCR8) involves in the progression of multiple cancers. However, the exact expression, function, and mechanism of DSCR8 in hepatocellular carcinoma (HCC) remain uncovered. In this study, real-time PCR in HCC tissues and cell lines indicated that DSCR8 expression was upregulated, while miR-485-5p was downregulated. MTT assay, plate clone formation, Edu assay, flow cytometry, and in vivo experiments indica ...[more]

PMID: 30154476

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Project description:BACKGROUND:Aberrant Wnt/?-catenin signaling is associated with breast cancer even though genetic mutations in Wnt signaling components are rare. We have previously demonstrated that Rad6B, an ubiquitin conjugating enzyme, stabilizes ?-catenin via polyubiqutin modifications that render ?-catenin insensitive to proteasomal degradation. Rad6B is a transcriptional target of ?-catenin, creating a positive feedback loop between Rad6B expression and ?-catenin activation. METHODS:To isolate subpopulations expressing high or low Rad6B levels, we transfected MDA-MB-231 or WS-15 human breast cancer cells with ZsGreen fluorescent reporter vector in which the expression of ZsGreen was placed under the control of Rad6B promoter. ZsGreenhigh and ZsGreenlow subpopulations, reflective of high and low Rad6B promoter activity, respectively, were isolated by FACS. To determine the relevance of Wnt signaling in Rad6B-mediated ?-catenin stabilization/activation, the ZsGreenhigh cells were transfected with signaling-defective Wnt coreceptor LRP6?173. Rad6B expression and promoter activity were determined by RT-PCR, Western blot and Rad6B promoter-mediated luciferase assays. ?-catenin levels and transcriptional activity were determined by Western blot and TOP/FOP Flash reporter assays. Tumor formation and morphologies of ZsGreenlow, ZsGreenhigh, and ZsGreenhigh/LRP6?173 cells compared to unsorted vector controls were evaluated in nude mice. Expression of Wnt signaling related genes was profiled using the Wnt signaling pathway RT2 Profiler PCR arrays. RESULTS:ZsGreenhigh subpopulations showed high Rad6B expression and Rad6B promoter activity as compared to ZsGreenlow cells. ZsGreenhigh (high Rad6B expressors) also showed elevated ?-catenin levels and TOP/Flash activity. Inhibiting Wnt signaling in the high Rad6B expressors decreased ZsGreen fluorescence, Rad6B gene expression, ?-catenin levels and TOP/Flash activity. Tumors derived from high Rad6B expressors were predominantly composed of cells with epithelial mesenchymal transition (EMT) phenotype as compared to control tumors that were composed of both cuboidal and EMT-type cells. Tumors derived from low Rad6B expressors lacked EMT phenotype. Inhibition of LRP6 function in the high Rad6B expressors abrogated the EMT phenotype. Gene expression profiling showed upregulation of several Wnt signaling pathway regulators in high Rad6B expressors that were downregulated by interference of Wnt signaling with mutant LRP6 or by Rad6B silencing. CONCLUSIONS:These data reveal a functional link between the canonical Wnt pathway and Rad6B in ?-catenin activation and breast cancer progression.

Dataset Information

Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/?-catenin signal pathway in hepatocellular carcinoma.

Publications

Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma.

Similar Datasets

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