Long noncoding RNA HOTAIR RNA HOTAIR promotes renal cell carcinoma malignancy through alpha‐2, 8‐sialyltransferase 4 by sponging micro RNA RNA ‐124

摘要

Abstract Objectives Accumulating evidence demonstrated that the long noncoding RNA (lnc RNA ) H OTAIR (Hox transcript antisense intergenic RNA ) plays key role in renal cell carcinoma ( RCC ) malignancy, while micro RNA ‐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 ( ST 8 SIA 4) axis‐regulated progression in RCC . Materials and methods Real‐time PCR analyses and western blots were performed to the levels of HOTAIR , miR‐124 and ST 8 SIA 4 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 ST 8 SIA 4 in tumorigenesis in vivo. Migration assays, invasion assays and cell adhesion assays and were also taken to analyse the carcinoma progression. Results In 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 ST 8 SIA 4 in RCC cell lines. ST 8 SIA 4 was upregulated in RCC tissues and RCC cell lines. Ectopic expression of ST 8 SIA 4 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 ST 8 SIA 4 expression by sponging miR‐124 in RCC . Conclusions Our results demonstrated that HOTAIR mediated RCC progression in part through miR‐124/ ST 8 SIA 4 axis, which functioned as a new prognostic biomarker in RCC .