Dataset Information

Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2? pathways in clear cell renal cell carcinoma cells.

ABSTRACT: Long non-coding RNAs (lncRNAs) have been proved to have an important role in different malignancies including clear cell renal cell carcinoma (ccRCC). However, their role in disease progression is still not clear. The objective of the study was to identify lncRNA-based prognostic biomarkers and further to investigate the role of one lncRNA LINC01234 in progression of ccRCC cells. We found that six adverse prognostic lncRNA biomarkers including LINC01234 were identified in ccRCC patients by bioinformatic analysis using The Cancer Genome Atlas database. LINC01234 knockdown impaired cell proliferation, migration and invasion in vitro as compared to negative control. Furthermore, the epithelial-mesenchymal transition was inhibited after LINC01234 knockdown. Additionally, LINC01234 knockdown impaired hypoxia-inducible factor-2a (HIF-2?) pathways, including a suppression of the expression of HIF-2?, vascular endothelial growth factor A, epidermal growth factor receptor, c-Myc, Cyclin D1 and MET. Together, these datas showed that LINC01234 was likely to regulate the progression of ccRCC by HIF-2? pathways, and LINC01234 was both a promising prognostic biomarker and a potential therapeutic target for ccRCC.

SUBMITTER: Yang F

PROVIDER: S-EPMC7568479 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2α pathways in clear cell renal cell carcinoma cells.

Yang Feilong F Liu Cheng C Zhao Guojiang G Ge Liyuan L Song Yimeng Y Chen Zhigang Z Liu Zhuo Z Hong Kai K Ma Lulin L

PeerJ 20201014

Long non-coding RNAs (lncRNAs) have been proved to have an important role in different malignancies including clear cell renal cell carcinoma (ccRCC). However, their role in disease progression is still not clear. The objective of the study was to identify lncRNA-based prognostic biomarkers and further to investigate the role of one lncRNA LINC01234 in progression of ccRCC cells. We found that six adverse prognostic lncRNA biomarkers including LINC01234 were identified in ccRCC patients by bioin ...[more]

PMID: 33088626

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Project description:Background:MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). Methods:The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. Results:we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. Conclusions:Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.

Dataset Information

Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2? pathways in clear cell renal cell carcinoma cells.

Publications

Long non-coding RNA LINC01234 regulates proliferation, migration and invasion via HIF-2α pathways in clear cell renal cell carcinoma cells.

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