bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2021‒08‒08
two papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

  1. Cell Signal. 2021 Jul 29. pii: S0898-6568(21)00190-X. [Epub ahead of print] 110101
      BACKGROUND: Septic acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. MicroRNA is reportedly involved in sepsis-induced organ dysfunction, while the role of miR-150 in septic AKI remains ambiguous.METHODS: Quantitative real-time PCR (qRT-PCR) was carried out to examine miR-150-5p expression in both septic AKI patients and volunteers without septic AKI. Lipopolysaccharide (LPS) was used to treat renal tubular epithelial cell line HK-2 and C57/BL6 mice to establish in vitro and in vivo sepsis-induced AKI models. Cell apoptosis was determined using TdT-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry. Cell viability was tested using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Renal pathological changes were examined via Hematoxylin-Eosin (H&E) staining, and renal function was measured via blood urea nitrogen (BUN) and creatinine (Cre) measurements. The MEKK3/JNK profile and oxidative stress markers (including COX2 and iNOS) were examined by immunoblot analysis, and the expression levels of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and oxidative stress markers (MDA, SOD, and CAT) were evaluated by ELISA.
    RESULTS: MiR-150-5p was down-regulated in the serum of patients with septic AKI (compared to healthy volunteers). Moreover, miR-150-5p levels were lower in LPS-treated HK-2 cell lines and in the septic AKI mouse model. Additionally, Stat-3 activation mediated the decrease of miR-150-5p. Functionally, miR-150-5p agomir attenuated LPS-induced apoptosis in HK-2 cells, in addition to renal inflammatory responses and oxidative stress. In contrast, inhibition of miR-150-5p aggravated LPS-induced apoptosis, inflammatory reactions and oxidative stress. Furthermore, miR-150-5p agomir decreased BUN and Scr levels in the septic AKI mice model repressed TNF-α, IL-6 and IL-1β, and up-regulated SOD and CAT down-regulated MDA in the kidney tissues. Moreover, miR-150-5p was identified as a target gene for Stat3, and the overexpression of Stat3 partially promoted the effect of down-regulating miR-150-5p on LPS-induced HK2 cell injury. Mechanistically, the MEKK3/JNK pathway was identified as a functional target of miR-150-5p, and the knockdown of MEKK3 showed protective effects against LPS mediated HK-2 cell apoptosis.
    CONCLUSION: Stat3-mediated miR-150-5p exerted protective effects in sepsis-induced acute kidney injury by regulating the MEKK3/JNK pathway.
    Keywords:  Acute kidney injury; JNK; Lipopolysaccharide; MEKK3; miR-150-5p
  2. Comput Math Methods Med. 2021 ;2021 5515218
      Urologic cancers, comprising prostate carcinoma (PCa), renal cell carcinoma (RCC), and bladder carcinoma (BCa), were the commonly occurred carcinoma amid males. Long noncoding RNAs (lncRNAs) with the length of more than 200 nt functioned importantly in physiological and pathological advancement. Nevertheless, further investigation regarding lncRNA expression feature and function in urologic cancers should be essential. This study is aimed at uncovering the roles of the differently expressed lncRNAs in urologic cancers. The data of gene expression levels was downloaded from lncRNAtor datasets. The lncRNA expression pattern existing in different urologic cancers was assessed by hierarchical clustering analysis. Gene Ontology (GO) analysis and KEGG pathway analysis were separately applied to evaluate the biological function and process and the biological pathways involving differently expressed lncRNAs. Our results indicated that 18 lncRNA expressions were increased, and 16 lncRNA expressions were reduced in urologic cancers after comparison with that in normal tissues. Moreover, our results demonstrated 61, 422, 137, and 281 lncRNAs were specifically dysregulated in bladder cancer (BLCA), kidney renal clear cell cancer (KIRC), kidney renal papillary cell cancer (KIRP), and prostate adenocarcinoma (PRAD), respectively. Bioinformatics analysis showed that differently expressed lncRNAs displayed crucially in urologic cancers. The prognostic value of common and cancer-specific differently expressed lncRNAs, such as PVT1, in cancer outcomes, was emphasized here. Our research has deeply unearthed the mechanism of differently expressed lncRNAs in urologic cancers development.