Abstract
Notwithstanding the researches on biomarkers and targeted therapies in renal cell carcinomas (RCC) have made progress in the last decades, the application of the biomarkers and targeted therapy agents for RCC in clinic are restricted because of their limitation or side effects. Liver X receptors (LXRs) and the NLRP3 inflammasome have been the research hotspots in recent years. In our study, we integrated bioinformatics analysis, molecular biology experiments and biological function experiments to study the roles of LXRα and the NLRP3 inflammasome in RCC. The study demonstrated that the elevated LXRα expression is correlated with a poor prognosis in RCC. Furthermore, our study revealed the expression levels and roles of the NLRP3 inflammasome in RCC for the first time. This research demonstrated that LXRα could promote the metastasis of RCC cells by suppressing the expression of the NLRP3 inflammasome. In Brief, LXRα had the possibility to be a novel diagnostic and prognostic biomarker and therapeutic target in renal cell cancer and LXRα could regulate the metastasis of renal cell cancer via NLRP3 inflammamsome.
Highlights
Renal cell carcinoma (RCC), characterized by high incidence and high mortality rates, constitutes 3% of adult malignancies
KaplanMeier curves indicated that high expression of LXRα or LXRβ predicted a poor prognosis in Clear-cell renal cell carcinoma (ccRCC) patients, and the overexpression of LXRα in ccRCC patients who were T1+T2 stage (p = 0.0105) or G1+G2 stage (p = 0.0146) was associated with a poor prognosis (Fig. 1c, Fig. S1B)
Our results indicated that the protein and mRNA expressions of LXRα were up-regulated in both ccRCC cells and tissues (Figs. 1e, f)
Summary
Renal cell carcinoma (RCC), characterized by high incidence and high mortality rates, constitutes 3% of adult malignancies. 20–30% RCC patients present with local or distant metastasis at the time of diagnosis, and the response to chemotherapy or radiotherapy in the majority of the. As a kind of nuclear receptor superfamily, the liver X receptor (LXR) family, including LXRα (LXRA, NR1H3) and LXRβ (LXRB, NR1H2), is an important regulator of several kinds of cancers (prostate cancer, breast cancer, etc.). While LXRβ is expressed widely throughout various tissues and organs, LXRα is mainly expressed in liver, kidney, spleen and intestine[5,6,7,8]. LXRs could influence the inflammatory response via regulating the expression of inflammatory cytokines, Official journal of the Cell Death Differentiation Association
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