bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2021‒05‒09
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

  1. Biochem Biophys Res Commun. 2021 Apr 28. pii: S0006-291X(21)00684-7. [Epub ahead of print]559 8-14
      BACKGROUND: Long non-coding RNAs (lncRNAs) play vital roles in human diseases, including sepsis-induced acute kidney injury (AKI). Here, we aimed to investigate the functions of lncRNA NKILA in sepsis-engendered AKI.METHODS: HK2 cells stimulated with LPS were used to mimic sepsis-induced AKI in vitro. qRT-PCR was conducted for lncRNA NKILA and miR-140-5p levels. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to analyze cell viability and apoptosis. Western blot assay was utilized to measured protein levels. ELISA kits were used to examine the concentrations of IL-6, IL-1β and TNF-α. Dual-luciferase reporter assay was utilized to analyze the relationships among lncRNA NKILA, miR-140-5p and claudin 2 (CLDN2).
    RESULTS: LPS restrained HK2 cell viability and accelerated cell apoptosis and autophagy. LncRNA NKILA was increased in LPS-treated HK2 cells. LncRNA NKILA silencing reversed the promotional influence of LPS on cell progression in HK2 cells. miR-140-5p inhibition ameliorated lncRNA NKILA knockdown-mediated cell injury in LPS-mediated HK2 cells. CLDN2 was the target of miR-140-5p. MiR-140-5p elevation promoted cell viability and suppressed cell apoptosis, autophagy and inflammation in LPS-induced HK2 cells, with CLDN2 elevation overturned the effects.
    CONCLUSION: LncRNA NKILA silencing protected HK2 cells from LPS-induced impairments by reducing CLDN2 through sponging miR-140-5p.
    Keywords:  CLDN2; HK2; LPS; lncRNA NKILA; miR-140-5p
  2. J Surg Res. 2021 May 03. pii: S0022-4804(21)00213-4. [Epub ahead of print]265 223-232
      BACKGROUND: Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the progression of sepsis-induced acute kidney injury (AKI). In this study, we aimed to explore the functions of lncRNA cancer susceptibility candidate 2 (CASC2) in sepsis-induced AKI.METHODS: The sepsis cell models were established by exposing HK2 and HEK293 cells into lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the expression of CASC2, miR-545-3p and peroxisome proliferator-activated receptor-α (PPARA) mRNA. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound healing assay were employed for cell viability, apoptosis and migration, respectively. Western blot assay was conducted for the protein levels of E-cadherin, α-SMA and PPARA. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by specific kits. The relationship between miR-545-3p and CASC2 or PPARA was verified by dual-luciferase reporter assay.
    RESULTS: CASC2 level was decreased in sepsis patients' serums and LPS-treated HK2 and HEK293 cells. CASC2 overexpression facilitated cell viability and restrained cell apoptosis, migration, epithelial-mesenchymal transition (EMT) and oxidative stress in LPS-triggered HK2 and HEK293 cells. CASC2 was identified as a sponge for miR-545-3p to regulate PPARA expression. MiR-545-3p overexpression restored the impact of CASC2 on LPS-induced injury in HK2 and HEK293 cells. Moreover, miR-545-3p overexpression aggravated LPS-induced cell injury in HK2 and HEK293 cells by targeting PPARA.
    CONCLUSION: CASC2 overexpression relieved the damage of HK2 and HEK293 cells mediated by LPS treatment through regulating miR-545-3p/PPARA axis.
    Keywords:  AKI; CASC2; MiR-545-3p; PPARA; Sepsis
  3. Biomolecules. 2021 Apr 29. pii: 664. [Epub ahead of print]11(5):
      LncRNA PVT1 (plasmacytoma variant translocation 1) has become a staple of the lncRNA profile in patients with renal cell carcinoma (RCC). Common dysregulation in renal tumors outlines the essential role of PVT1 in the development of RCC. There is already a plethora of publications trying to uncover the cellular mechanisms of PVT1-mediated regulation and its potential exploitation in management of RCC. In this review, we summarize the literature focused on PVT1 in RCC and aim to synthesize the current knowledge on its role in the cells of the kidney. Further, we provide an overview of the lncRNA profiling studies that have identified a more or less significant association of PVT1 with the clinical behavior of RCC. Based on our search, we analyzed the 17 scientific papers discussed in this review that provide robust support for the indispensable role of PVT1 in RCC development and future personalized therapy.
    Keywords:  biomarker; diagnosis; long non-coding RNA; prognosis; tumorigenesis
  4. Genetics. 2019 Dec 01. 213(4): 1093-1110
      Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate specification of cell types to replace damaged/diseased tissue is strongly dependent on identifying determinants of cell identity. Long noncoding RNAs (lncRNAs) have been shown to regulate cellular plasticity, including pluripotency establishment and maintenance, differentiation and development, yet broad phenotypic analysis and the mechanistic basis of their function remains lacking. As components of molecular condensates, lncRNAs interact with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs. With functions ranging from controlling alternative splicing of mRNAs, to providing scaffolding upon which chromatin modifiers are assembled, it is clear that at least a subset of lncRNAs are far from the transcriptional noise they were once deemed. This review highlights the diversity of lncRNA interactions in the context of cell fate specification, and provides examples of each type of interaction in relevant developmental contexts. Also highlighted are experimental and computational approaches to study lncRNAs.
    Keywords:  cell fate specification; competing endogenous RNAs; k-mers; long noncoding RNAs; miRNAs