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Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

ABSTRACT: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.

SUBMITTER: Bravo-Vazquez LA

PROVIDER: S-EPMC10815231 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

Bravo-Vázquez Luis Alberto LA Paul Sujay S Colín-Jurado Miriam Guadalupe MG Márquez-Gallardo Luis David LD Castañón-Cortés Luis Germán LG Banerjee Antara A Pathak Surajit S Duttaroy Asim K AK

Genes 20240119 1

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this cont ...[more]

PMID: 38275604

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Project description:Renal fibrosis is the hallmark of virtually all progressive kidney diseases and strongly correlates with the deterioration of kidney function. The renin-angiotensin-aldosterone system blockade is central to the current treatment of patients with chronic kidney disease (CKD) for the renoprotective effects aimed to prevent or slow progression to end-stage renal disease (ESRD). However, the incidence of CKD is still increasing, and there is a critical need for new therapeutics. Here, we review novel strategies targeting various components implicated in the fibrogenic pathway to inhibit or retard the loss of kidney function. We focus, in particular, on antifibrotic approaches that target transforming growth factor (TGF)-β1, a key mediator of kidney fibrosis, and exciting new data on the role of autophagy. Bone morphogenetic protein (BMP)-7 and connective tissue growth factor (CTGF) are highlighted as modulators of profibrotic TGF-β activity. BMP-7 has a protective role against TGF-β1 in kidney fibrosis, whereas CTGF enhances TGF-β-mediated fibrosis. We also discuss recent advances in the development of additional strategies for antifibrotic therapy. These include strategies targeting chemokine pathways via CC chemokine receptors 1 and 2 to modulate the inflammatory response, inhibition of phosphodiesterase to restore nitric oxide-cyclic 3',5'-guanosine monophosphate function, inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4 to suppress reactive oxygen species production, and inhibition of endothelin 1 or tumor necrosis factor α to ameliorate progressive renal fibrosis. Furthermore, a brief overview of some of the biomarkers of kidney fibrosis is currently being explored that may improve the ability to monitor antifibrotic therapies. It is hoped that evidence based on the preclinical and clinical data discussed in this review leads to novel antifibrotic therapies effective in patients with CKD to prevent or delay progression to ESRD.

Project description:Kidney renal clear cell carcinoma (KIRC) is considered an immunogenic tumor. Cuproptosis is a newly identified copper-induced regulated cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) have emerged as significant players in tumorigenesis and metastasis. However, there is a huge knowledge gap on the prognostic role of cuproptosis-related lncRNAs in KIRC. And, the clinical value of them is still unknown. Here, we aimed to develop a cuproptosis-related lncRNA prognostic signature in KIRC. The messenger RNA (mRNA)/lncRNA expression profiles and the clinical information including age, gender, tumor stage, grade, and overall survival (OS) were acquired from The Cancer Genome Atlas (TCGA) database. The included KIRC samples were further randomly assigned into training (n=258) or testing (n=257) data sets. We performed Pearson correlation analysis to identify the cuproptosis-related lncRNAs and then constructed the prognostic signature using Cox regression analysis and LASSO algorithm. Subsequently, Kaplan-Meier survival analysis, a nomogram, and receiver operating characteristic (ROC) curve were performed to assess the predictive performance of the signature. Moreover, the immune characteristics and drug sensitivity related to the signature were also explored. The signature comprised 7 cuproptosis-related lncRNAs. The patients with a low-risk score had superior OS compared with those with a high-risk score. The survival rates of the high- and low-risk groups were 44.96% and 83.72% (P<0.001). The area under the curve (AUC) value for 1-, 3-, 5-year survival rate reached 0.814, 0.762 and 0.825, respectively. In addition, a nomogram was also generated; the AUC was 0.785 for risk score, higher than that for age (0.593), gender (0.489), grade (0.679), and stage (0.721). The high-risk group had more enriched immune- and tumor-related genes. Patients with low-risk scores were more sensitive to immunotherapy and the small molecular drugs GSK1904529A, tipifarnib, BX-912, FR-180204, and GSK1070916. Meanwhile, the high-risk group tended to be more sensitive to pyrimethamine, MS-275, and CGP-60474. Collectively, we constructed a cuproptosis-related lncRNA prognostic signature with a higher predictive accuracy compared to multiple clinicopathological parameters, which may provide vital guidance for therapeutic strategies in KIRC. Combination of more prognostic biomarkers may further improve the accuracy.

Dataset Information

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

Publications

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

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