RNA‐Seq analysis of potential lncRNAs and genes for the anti‐renal fibrotic effect of norcantharidin

Abstract

Background As a common phenotype in chronic kidney disease, renal interstitial fibrosis has been largely studied. Norcantharidin (NCTD), a derivative of naturally occurring cantharidin, has an anti‐renal fibrotic effect. However, its underlying mechanisms of the protective role remain largely unknown. Long noncoding RNAs (lncRNAs) play vital parts in tissue homeostasis modulation under pathophysiological conditions. In this study, we discovered the underlying lncRNAs and genes, which may contribute to the anti‐renal fibrotic effects of NCTD. Methods RNA‐seq analysis was performed to evaluate profiling of lncRNAs and messenger RNAs (mRNAs) in kidney tissues of sham‐control, and unilateral ureteral obstruction (UUO) mouse models with or without NCTD treatment. Systematic bioinformatic analysis of expression levels was used in lncRNAs and mRNAs of NCTD‐treated UUO kidneys. Altered expression of lncRNAs and mRNAs levels was confirmed by quantitative real‐time polymerase chain reaction analysis. Results 467 lncRNAs and 1502 mRNAs were differentially expressed between UUO‐ and sham‐operated kidneys, and notably, these alterations in UUO‐operated kidney were partially reversed following NCTD treatment. Interestingly, the up‐regulation of lncRNA Gm16076, Gm26669, and down‐regulation of Fam120aos were highly correlated with the up‐regulation of mRNA levels of fibrosis‐related gene ITGB1, STAT3 and reduction of Pink1 in UUO kidney, respectively. Conclusions The result suggested lncRNAs‐regulated genes may contribute to the anti‐renal fibrotic effect under NCTD treatment, and thus targeting lncRNAs‐controlled genes and their related molecular signaling pathways may serve as a promising therapeutic target in renal fibrosis treatment.

Anti‐renal interstitial fibrosis effect of norcantharidin is exerted through inhibition of PP2Ac‐mediated C‐terminal phosphorylation of Smad3

“…Norcantharidin is a widely used agent in cancer chemotherapy (Deng & Tang, 2011). Our previous studies showed that NCTD suppressed RIF both in vitro and in vivo renal fibrosis models (Li, Chen, Liu, Peng, Hou, et al, 2011; Li, Chen, Liu, Peng, Wang, et al, 2011; Li et al., 2012, 2013; Liu et al., 2008; Xiao et al., 2019). Here, we found that TGF‐β1‐induced Fn expression was abrogated by NCTD in HK‐2 cells, which was in agreement with previous studies and provide further evidence for the anti‐fibrotic effect of NCTD.…”

“…NCTD is widely used in the treatment of liver and stomach cancers and other gastrointestinal tumors (Deng & Tang, 2011). In previous studies, we showed that NCTD effectively suppressed RIF (Li, Chen, Liu, Peng, Hou, et al, 2011; Li, Chen, Liu, Peng, Wang, et al, 2011; Liu et al., 2008; Xiao et al., 2019).…”

LncRNA SNHG1 promotes EMT process in gastric cancer cells through regulation of the miR-15b/DCLK1/Notch1 axis

“…Studies have found that lncRNA is involved in many life activities such as the dose compensation effect, and it has become a hot topic in genetic research [30][31][32]. Many studies have reported that lncRNA is involved in regulating the progression of malignant tumours [33].…”

Non-Coding RNAs in Kidney Diseases: The Long and Short of Them

“…Additional urine analysis reported upregulation of 625 lncRNAs and downregulation of 177 lncRNAs, some of which (NONRATT044682, 361619 and 689064) could be possible biomarkers of renal fibrosis. In another study, lncRNAs Gm10251, Fam120aos and Gm16076 regulated the Jak/STAT pathway, whereas lncRNAs Fam12aos and Gm16076 interacted with fibroblast integrin beta1 (ITGB1) [ 64 ]. The lncRNA 74.1 was downregulated in HK-2 cells exposed to TGF-β.…”