Puri Bhupendra, Majumder Syamantak, Gaikwad Anil Bhanudas
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
Department of Biological Sciences, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
Pathol Res Pract. 2025 Feb;266:155783. doi: 10.1016/j.prp.2024.155783. Epub 2024 Dec 20.
Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript1 (MALAT1) has emerged as a crucial biomarker and therapeutic target for kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and renal cell carcinoma (RCC). LncRNAs are non-coding RNAs that have more than 200 nucleotides that play a crucial role in gene regulation at the post-translational stage, transcriptional, and epigenetic levels. LncRNA MALAT1 regulates gene expression and modulates cellular functions such as proliferation, inflammation, apoptosis, and fibrosis, which are key pathophysiology of kidney diseases. Overexpression of lncRNA MALAT1 has been consistently observed in kidney tissue, correlating with the severity and progression of kidney disease. In AKI, lncRNA MALAT1 exacerbates inflammation and tissue damage, contributing to disease progression. In CKD and DKD, lncRNA MALAT1 is implicated in the regulation of fibrosis by modulating key pathways, including focal adhesion kinase (FAK), toll-like receptor 4 (TLR4), NOD-like receptor protein3 (NLRP3), and nuclear factor kappa B (NF-κB), play pivotal roles in promoting disease progression. In LN, lncRNA MALAT1 has been linked to immune regulation and kidney damage, while in RCC, its role in promoting tumor growth and metastasis has been well documented. Preclinical research has demonstrated that therapeutic strategies targeting lncRNA MALAT1, such as knockdown and knockout, can reduce inflammation and fibrosis while improving kidney function. The fundamental role of lncRNA MALAT1 in kidney disease progression is yet to be fully understood. However, lncRNA MALAT1 has shown promise as a biomarker and therapeutic target to mitigate kidney disease development. This review highlights the potential of lncRNAs MALAT1 as diagnostic biomarkers and therapeutic targets, offering insights into a comprehensive approach to managing kidney diseases in the future.
长链非编码RNA(lncRNA)转移相关肺腺癌转录本1(MALAT1)已成为肾脏疾病的关键生物标志物和治疗靶点,这些疾病包括急性肾损伤(AKI)、慢性肾脏病(CKD)、糖尿病肾病(DKD)、狼疮性肾炎(LN)和肾细胞癌(RCC)。lncRNAs是具有超过200个核苷酸的非编码RNA,在翻译后阶段、转录和表观遗传水平的基因调控中发挥关键作用。lncRNA MALAT1调节基因表达并调节细胞功能,如增殖、炎症、凋亡和纤维化,这些都是肾脏疾病的关键病理生理学过程。在肾组织中一直观察到lncRNA MALAT1的过表达,这与肾脏疾病的严重程度和进展相关。在急性肾损伤中,lncRNA MALAT1会加剧炎症和组织损伤,促进疾病进展。在慢性肾脏病和糖尿病肾病中,lncRNA MALAT1通过调节关键信号通路参与纤维化调控,这些通路包括粘着斑激酶(FAK)、Toll样受体4(TLR4)、NOD样受体蛋白3(NLRP3)和核因子κB(NF-κB),它们在促进疾病进展中起关键作用。在狼疮性肾炎中,lncRNA MALAT1与免疫调节和肾脏损伤有关,而在肾细胞癌中,其在促进肿瘤生长和转移中的作用已有充分记录。临床前研究表明,针对lncRNA MALAT1的治疗策略,如敲低和敲除,可以减轻炎症和纤维化,同时改善肾功能。lncRNA MALAT1在肾脏疾病进展中的基本作用尚未完全了解。然而,lncRNA MALAT1已显示出作为减轻肾脏疾病发展的生物标志物和治疗靶点的潜力。本综述强调了lncRNAs MALAT1作为诊断生物标志物和治疗靶点的潜力,为未来全面管理肾脏疾病提供了见解。