LncRNA HOTAIR regulates HIF-1|[alpha]||[sol]|AXL signaling through inhibition of miR-217 in renal cell carcinoma
CELL DEATH & DISEASE(2017)
摘要
Long non-coding RNA HOTAIR was regarded as an oncogene in multiple cancers. Previous studies have shown that HOTAIR is involved in the proliferation and tumorigenesis of renal carcinoma cells, while microRNA (miR)-217 functions as a tumor suppressor in renal cell carcinoma (Rcc). However, the underlying molecular mechanism of HOTAIR in Rcc, especially in association with miR-217, has not been studied. In this study, we first demonstrated that HOTAIR expression was upregulated, which was correlated with tumor progression, and miR-217 downregulated in Rcc tissues and cells. Importantly, HOTAIR expression was negatively correlated with miR-217 expression in Rcc tissues. Gain-and loss-of-function of HOTAIR revealed that HOTAIR functioned as a ceRNA for miR-217 to facilitate HIF-1 alpha expression and then upregulated AXL level promoting Rcc proliferation, migration, and EMT process, and inhibiting apoptosis. Furthermore, HOTAIR knockdown suppressed tumor growth and reduced the expression of proliferation antigen ki-67, HIF-1 alpha, and AXL, but upregulated the expression of miR-217 in vivo. Finally, with AXL inhibitor BGB324, we confirmed that HOTAIR promoted Rcc activity through AXL signaling both in vitro and in vivo. In conclusion, these results suggest that HOTAIR promotes Rcc tumorigenesis via miR-217/HIF-1 alpha/AXL signaling, which may provide a new target for the diagnosis and therapy of Rcc disease.
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关键词
cancer,immunity,neurodegeneration,apoptosis,cell death,cell growth,Stem Cell,Signaling,Autophagy,Wallerian Degeneration,Cornification,Keratinization,Toxicity,Transcription
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