Research Paper Advance Articles
A regulatory circuit of lncRNA NLGN1-AS1 and Wnt signalling controls clear cell renal cell carcinoma phenotypes through FZD4-modulated pathways
- 1 Department of Urology, Binhai County People’s Hospital, Yancheng 224500, China
- 2 Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
- 3 Department of Urology, Yancheng Third People’s Hospital, Yancheng 224000, China
- 4 Department of Oncology, Huaian Hospital of Huaian City, Huai’an 223200, China
Received: May 13, 2022 Accepted: August 23, 2022 Published: September 27, 2022https://doi.org/10.18632/aging.
How to Cite
Copyright: © 2022 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.