Rs145204276 polymorphism of GAS5 is associated with renal fibrosis via miR-21/SMAD/TGF-β1 signaling pathway
Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), has been identified as a key gene expression regulator in multiple cancers. The polymorphism of the promoter region of GAS5 promotes the transcription level of GAS5, and then supervises its downstream signal pathway. This study was designed to investigate the mechanism between GAS5 and renal fibrosis. Results: rs145204276 polymorphism (INS or DEL allele) located in promoter of GAS5. The DEL/DEL of GAS5 promotes the transcription
... the transcription of GAS5 and lower Histological score of kidneys disease samples. QRTPCR of clinical sample show that the DEL/DEL genotype group displayed higher levels of GAS5 and SMAD7 mRNA, and lower levels of miR-21 and TGFB1 protein than INS/INS group. Further mechanism study show that GAS5 inhibits the expression level of miR-21 and then the miR-21/SMAD7/SMAD3 feedback loop. Our further study confirmed that the expression of GAS5 supervised the expression of miR21, SMAD7 and TGFB1. Meanwhile, SMAD7 is a directly target gene of miR-21. Materials and Methods: Bioinformatics analysis and luciferase assay were employed to investigate the role of rs145204276 polymorphism in gene expression regulation. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and westernblot were employed to study the expression level. Hematoxylin-eosin staining was performed to explore role of rs145204276 polymorphism of GAS5 in renal fibrosis. Conclusions: our study shows that GAS5 (lncRNAs) supervises SMAD/TGF-β1 -mediated renal fibrosis via miR-21. In addition, rs145204276 polymorphism (INS or DEL allele) of GAS5 contributes to renal fibrosis via transcription of the GAS5, and then serves as a potential therapeutic target for renal fibrosis.