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The lncRNA SNHG5-mediated miR-205-5p downregulation contributes to the progression of clear cell renal cell carcinoma by targeting ZEB1.

ABSTRACT: Recent findings have unraveled the critical functions of the long noncoding RNA (lncRNA) SNHG5 in human malignancies. Nevertheless, the role and mechanism of SNHG5 in clear cell renal cell carcinoma (ccRCC) are still elusive. In our study, substantially higher abundance of SNHG5 was observed in ccRCC specimens and cell lines, and increased SNHG5 expression was intimately correlated with tumor size, tumor-node-metastasis (TNM) stage, lymph node invasion, and distant metastases in patients with ccRCC. SNHG5 knockdown obviously suppressed the proliferative, migratory, and invasive capabilities of ccRCC cells, whereas SNHG5 overexpression induced the opposite effects. Mechanistically, SNHG5 activated the transcription of ZEB1, which exerts a pivotal role in modulation of epithelia-mesenchymal transition (EMT) and tumor metastasis. SNHG5 was then shown to act as an endogenous sponge for miR-205-5p, which targets ZEB1 in ccRCC. Moreover rescue experiments revealed that SNHG5 promotes ccRCC cell proliferation, migration, and invasion in a miR-205-5p-dependent manner. Additionally, in vivo assays further indicated that overexpression or silencing of SNHG5 in ccRCC cells promoted or suppressed the tumorigenesis and metastasis, respectively. Altogether, the present data provide the first evidence that the lncRNA SNHG5 has an oncogenic role in ccRCC through the SNHG5/miR-205-5p/ZEB1 signaling axis and represents a novel potential therapeutic regimen against ccRCC.

SUBMITTER: Xiang W

PROVIDER: S-EPMC7300396 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The lncRNA SNHG5-mediated miR-205-5p downregulation contributes to the progression of clear cell renal cell carcinoma by targeting ZEB1.

Xiang Wei W Lv Lei L Zhou Gaofeng G Wu Wei W Yuan Jingdong J Zhang Chuanhua C Jiang Guosong G

Cancer medicine 20200412 12

Recent findings have unraveled the critical functions of the long noncoding RNA (lncRNA) SNHG5 in human malignancies. Nevertheless, the role and mechanism of SNHG5 in clear cell renal cell carcinoma (ccRCC) are still elusive. In our study, substantially higher abundance of SNHG5 was observed in ccRCC specimens and cell lines, and increased SNHG5 expression was intimately correlated with tumor size, tumor-node-metastasis (TNM) stage, lymph node invasion, and distant metastases in patients with cc ...[more]

PMID: 32281285

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Project description:ObjectiveThe aim of this study was to explore expression profiles of long noncoding RNA (lncRNA)-messenger RNA (mRNA) in abdominal aortic aneurysm (AAA) patients. Further, we explored the mechanisms by which lncRNA SNHG5 modulates the function of vascular smooth muscle cells (VSMC) in AAA.MethodsHuman gene expression profile GSE57691 dataset, was retrieved from Gene Expression Omnibus database. The dataset included gene expression array data of 49 AAA patients and 10 control aortic specimens from organ donors. To explore the main roles of the biological network, differentially expressed lncRNA and mRNAs in the aortic aneurysm (AAA) and normal aortic specimens were determined. Differentially expressed lncRNA and mRNAs were then used to construct a competing endogenous RNA (ceRNA) network using Cytoscape software, and the five key lncRNA were identified. SNHG5 which was significantly downregulated in the AAA was chosen and analysis showed that it regulates mir-205-5p and SMAD4 by binding to mir-205-5p. Double luciferase reporter gene assays, RNA immunoprecipitation, and RNA knockdown studies were used to establish the relationship between SNHG5 and mir-205-5p. Apoptosis rate was determined using flow cytometry, whereas cell proliferation was evaluated using Edu, and 24 well Transwell assay. Western blot analysis was used to determine protein expression levels.ResultsThe five differentially expressed lncRNAs were significantly correlated with 34 microRNAs and 112 mRNAs. mRNAs in the ceRNA network are implicated in protein binding, signal transduction, DNA and RNA transcription, development, and cell differentiation. SNHG5 was downregulated in the AAA and acts as a molecular sponge for mir-205. Downregulation of SNHG5 induces expression of mir-205-5p. Increased mir-205-5p expression level inhibits SMAD4 production, thus inhibiting proliferation and migration and promotes apoptosis of smooth muscle cells.ConclusionBioinformatics were used to explore molecular mechanism of AAA progression. The findings of this study show that lncRNA SNHG5 regulates proliferation and apoptosis of VSMC cells through modulation of the mir-205-5p/SMAD4 axis. Therefore, SNHG5 is a potential therapeutic target for AAA disease.

Dataset Information

The lncRNA SNHG5-mediated miR-205-5p downregulation contributes to the progression of clear cell renal cell carcinoma by targeting ZEB1.

Publications

The lncRNA SNHG5-mediated miR-205-5p downregulation contributes to the progression of clear cell renal cell carcinoma by targeting ZEB1.

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