bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2022–03–13
two papers selected by
Nikita Dewani, Max Delbrück Centre for Molecular Medicine
  1. LncRNA NORAD deficiency alleviates kidney injury in mice and decreases the inflammatory response and apoptosis of lipopolysaccharide-stimulated HK-2 cells via the miR-577/GOLPH3 axis.
  2. Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2.
  1. Cytokine. 2022 Mar 04. pii: S1043-4666(22)00053-9. [Epub ahead of print]153 155844
    LncRNA NORAD deficiency alleviates kidney injury in mice and decreases the inflammatory response and apoptosis of lipopolysaccharide-stimulated HK-2 cells via the miR-577/GOLPH3 axis.
    Zhijuan Xie, Lanji Wei, Jianying Chen, Zhong Chen.
       BACKGROUND: Long noncoding RNAs (lncRNAs) are significant regulators for sepsis-associated acute kidney injury (AKI). Noncoding RNA activated by DNA damage (NORAD) is highly expressed in the serum of patients with neonatal sepsis. We aimed to reveal the role of NORAD in sepsis-associated AKI.
    METHODS AND RESULTS: In this study, we established an AKI mouse model by cecal ligation and puncture (CLP) method and used the lipopolysaccharide (LPS)-stimulated HK-2 cells as the in vitro model of AKI. We identified the upregulation of NORAD expression in AKI mice and LPS-treated HK-2 cells. Silencing of NORAD alleviated renal injury by suppressing inflammation and apoptosis in vivo. The influences of NORAD suppression on cell apoptosis and inflammatory response in LPS-treated HK-2 cells were investigated by TUNEL and western blotting. NORAD deficiency inhibited HK-2 cell apoptosis and relieved the inflammation. Moreover, we explored the underlying mechanism by which NORAD regulates HK-2 cells. MiR-577 was verified to directly bind to NORAD, and GOLPH3 was identified as a target downstream miR-577. In addition, GOLPH3 overexpression countervailed the impacts of NORAD downregulation on apoptosis and inflammation in vitro.
    CONCLUSIONS: Our findings revealed that NORAD knockdown alleviates kidney injury in mice and decreases the inflammatory response and apoptosis of LPS-stimulated HK-2 cells via the miR-577/GOLPH3 axis.
    Keywords:  Acute kidney injury; GOLPH3; NORAD; Sepsis; miR-577
    DOI:  https://doi.org/10.1016/j.cyto.2022.155844
  2. Kaohsiung J Med Sci. 2022 Mar 08.
    Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2.
    Gang Zhang, Song-Lin Liu, Wen-Ting Yi, Yu-Ping Dong, Yin-Xu Wan.
      Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.
    Keywords:  ESCO2; RCC; ZFPM2-AS1; miR-130a-3p
    DOI:  https://doi.org/10.1002/kjm2.12527
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