Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.
The metabolic dysregulation is a hallmark of cancers including KIRC, specifically caused by alterations in metabolic genes. Currently, a lack of consensus exists between metabolic signatures in the tumor microenvironment. Here, in this study, we observed the significant correlations of differentially expressed metabolic genes (DEmGs) between KIRC and the related normal samples. Briefly, we collected sets of metabolic genes through RNA-seq data of KIRC and normal tissues from TCGA, followed by the identification of KIRC-related DEmGs. Next, patients were classified into three clusters, and using WGCNA, we identified metabolic genes involved in the survival among different clusters. Furthermore, we investigated survival and clinical parameters along with immune infiltration in the clusters. At the same time, we constructed and validated a prediction model based on these DEmGs. These analyses revealed that the patients having high expression of DEmGs showed poor survival, while infiltration of less-immune cells was associated with the metastasis of KIRC. In the end, we identified NUDT1 as a hub gene as it showed significantly high expression in KIRC samples as well as associated with the survival and prognosis of the patients. Further analysis revealed the oncogenic role of NUDT1 in 786-O and ACHN cells. Thus, we conclude that NUDT1 could be a potential diagnostic and prognostic marker for KIRC.
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