%A Gao, Haifeng 
%A Chen, Wei 
%A Pan, Gaojian 
%A Liu, Hui 
%A Qian, Jinke 
%A Tang, Weijun 
%A Wang, Wei 
%A Qian, Shilei 
%D 2022
%T A regulatory circuit of lncRNA NLGN1-AS1 and Wnt signalling controls clear cell renal cell carcinoma phenotypes through FZD4-modulated pathways
%! A regulatory circuit of lncRNA NLGN1-AS1 and Wnt signalling controls clear cell renal cell carcinoma phenotypes through FZD4-modulated pathways
%K clear cell renal cell carcinoma, long noncoding RNA, NLGN1-AS1, proliferation, Wnt/β-catenin pathway
%X Background: Recent evidence has indicated that long non-coding RNAs (lncRNAs) were emerged as key molecules in clear cell renal cell carcinoma (ccRCC). TCGA database showed that the expression level of lncRNA NLGN1-AS1 was up-regulated in ccRCC; However, whether NLGN1-AS1 implicated in the malignant progression of ccRCC remained unclear.
Methods: Based on TCGA database, candidate lncRNAs were selected and quantitative real-time PCR (qRT-PCR) was utilized to verify the expression levels of candidate lncRNAs in human ccRCC tissues. Loss-of-function experiments were performed to examine the biological functions of NLGN1-AS1 both in vitro and in vivo. According to bioinformatics analysis, fluorescence reporter assays and rescue experiments, the underlying mechanisms of NLGN1-AS1 in ccRCC cell lines were so clearly understood.
Results: As a novel lncRNA, NLGN1-AS1 was up-regulated in ccRCC cell lines and associated with poor prognosis of and ccRCC patients, which was correlated with the progression of ccRCC. Functionally, the down-regulation of NLGN1-AS1 significantly decreased the proliferation of ccRCC cells both in vitro and in vivo. Bioinformatics analysis and luciferase report assays identified that miR-136-5p was a direct target of NLGN1-AS1. We also determined that FZD4 were inhibitory targets of miR-136-5p, and that Wnt/β-catenin signaling was inhibited by both NLGN1-AS1 knockdown and miR-136-5p over-expression. In addition, we found that the suppression of proliferation and the inhibition of Wnt/β-catenin pathway induced by NLGN1-AS1 knockdown would require the over-expression of FZD4.
Conclusions: Our findings suggested that lncRNA NLGN1-AS1 could promote the progression of ccRCC by targeting miR-136-5p/FZD4 and Wnt/β-catenin pathway, and might serve as a novel potential therapeutic target to inhibit the progression of ccRCC.
%U https://doi.org/10.18632/aging.204263
%J Aging
%0 Journal Article
%V 15
%N 24
%P 15624-15639
%R 10.18632/aging.204263
%@ 1945-4589