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The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma.

ABSTRACT: The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

SUBMITTER: Hu G

PROVIDER: S-EPMC5601682 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma.

Hu Guanghui G Dong Binbin B Zhang Jingwei J Zhai Wei W Xie Tiancheng T Huang Bisheng B Huang Chi C Yao Xudong X Zheng Junhua J Che Jianping J Xu Yun-Fei YF

Oncotarget 20170425 35

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth <i>in vitro</i> and <i>in vivo</i>. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOT ...[more]

PMID: 28938586

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Project description:ObjectivesAccumulating evidence demonstrated that the long noncoding RNA (lncRNA) HOTAIR (Hox transcript antisense intergenic RNA) plays key role in renal cell carcinoma (RCC) malignancy, while microRNA-124 (miR-124) is a tumour suppressor in RCC. The aim of this work was to assess the biological function of HOTAIR and to explore underlying mechanism involved in HOTAIR/miR-124/alpha-2, 8-sialyltransferase 4 (ST8SIA4) axis-regulated progression in RCC.Materials and methodsReal-time PCR analyses and western blots were performed to the levels of HOTAIR, miR-124 and ST8SIA4 expression in human RCC tissues and RCC cell lines (ACHN and 786-O). Bioinformatics analysis and dual-luciferase reporter assay were used to illustrate relationship between HOTAIR and miR-124 in RCC. Colony formation assays, EdU assays, Ki67 assays and apoptosis assays were taken to evaluate cell proliferation. Tumour xenograft was created to explore the functions of HOTAIR and ST8SIA4 in tumorigenesis in vivo. Migration assays, invasion assays and cell adhesion assays and were also taken to analyse the carcinoma progression.ResultsIn this study, HOTAIR level was confirmed to be significantly upregulated in RCC samples and RCC cell lines compared with those in the paired adjacent tissues and normal renal cell line. Overexpression of HOTAIR promoted the capability of proliferation, migration and invasion in RCC cell lines. HOTAIR directly bound to miR-124, while miR-124 mediated the expression of ST8SIA4 in RCC cell lines. ST8SIA4 was upregulated in RCC tissues and RCC cell lines. Ectopic expression of ST8SIA4 modulated the proliferation, migration and invasion of RCC cells. Further results indicated that HOTAIR promoted the proliferation and metastasis as a competing endogenous RNA to regulate ST8SIA4 expression by sponging miR-124 in RCC.ConclusionsOur results demonstrated that HOTAIR mediated RCC progression in part through miR-124/ST8SIA4 axis, which functioned as a new prognostic biomarker in RCC.

Dataset Information

The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma.

Publications

The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma.

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