bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020‒11‒08
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine


  1. FASEB J. 2020 Nov 04.
    Zhao P, Deng Y, Wu Y, Guo Q, Zhou L, Yang X, Wang C.
      Recent studies have showed that Small nucleolar RNA host genes (SNHGs) acted as a subset of long noncoding RNAs (lncRNAs) have critical roles in human cancer carcinogenesis. However, the biological functions of SNHGs in clear cell renal cell carcinoma (ccRCC) have not been fully investigated. In this study, we screened an oncogenic lncRNA termed SNHG6 using RNA-Seq data of ccRCC from The Cancer Genome Atlas (TCGA). Quantitative real-time PCR was then used to demonstrate the expression of SNHG6 in ccRCC tissues. SNHG6 overexpression is highly associated with malignant features in patients and is a prognostic indicator. SNHG6 significantly promotes ccRCC cell proliferation and metastasis in vitro and in vivo. Mechanistic investigations identified that SNHG6 exerts oncogenic effects by interacting with YBX1, and then, enhancing HIF1α translation. Taken together, SNHG6 promotes ccRCC progression by binding YBX1 and may serve as a novel molecular target for ccRCC therapy.
    Keywords:  SNHG6; YBX1; clear cell renal cell carcinoma
    DOI:  https://doi.org/10.1096/fj.202000732RR
  2. Am J Physiol Renal Physiol. 2020 Nov 02.
    Zhang B, Zhao C, Hou L, Wu Y.
      Renal interstitial fibrosis (RIF) is characterized by excessive extracellular matrix deposition and involves epithelial-mesenchymal transition (EMT). The long non-coding RNA TUG1 participates in EMT in several cancers; however, the effect and underlying mechanism of TUG1 in RIF-related EMT remain unclear. Here, we explored the mechanisms by which TUG1 modulated RIF. An in vivo model of renal fibrosis was established through unilateral ureteral obstruction in Balb/c mice. Human renal proximal tubular epithelial (HK-2) cells treated with transforming growth factor (TGF)-β1 were used to induce the in vitro model. Morphological changes and TUG1 expression were assessed. HK-2 cells were transfected with a small interfering RNA to silence TUG1. Western blotting, immunofluorescence staining, cell proliferation, and migration assays were performed to examine TGF-β1-induced changes in EMT markers and EMT-like cell behaviors. TUG1 and β-catenin levels were significantly upregulated while miR-141-3p was obviously downregulated during EMT in vitro and in vivo. TUG1 knock-down or miR-141-3p overexpression supported the epithelioid morphology of HK-2 cells while enhancing the downregulation of E-cadherin and upregulation of vimentin, alpha-smooth muscle actin (α-SMA), and β-catenin levels in TGF-β1-treated HK-2 cells. TUG1 knock-down promoted the proliferation, while decreasing the migration, of HK-2 cells and enhanced the downregulation of miR-141-3p level in TGF-β1-treated HK-2 cells. TUG1 directly targeted miR-141-3p, and miR-141-3p was directly bound to CTNNB1. Downregulation of miR-141-3p inhibited TUG1-silencing-induced suppression of EMT. In conclusion, TUG1 promotes EMT in TGF-β1-induced HK-2 cells by upregulating β-catenin levels through sponging miR-141-3p, suggesting a novel therapeutic candidate for RIF.
    Keywords:  epithelial-mesenchymal transition; lncRNA TUG1; miR-141-3p; renal interstitial fibrosis; β-catenin
    DOI:  https://doi.org/10.1152/ajprenal.00321.2020
  3. Eur Rev Med Pharmacol Sci. 2020 Oct;pii: 23394. [Epub ahead of print]24(20): 10426-10432
    Zhao W, Wang L, Xu F.
      OBJECTIVE: The purpose of this study was to clarify the potential role of long non-coding RNA (lncRNA) NORAD in the development of renal cancer.PATIENTS AND METHODS: Expression levels of NORAD, miR-144-3p, and MYCN in renal cancer tissues and cell lines were detected. After overexpression of NORAD, proliferative and migratory changes in ACHN and A498 cells were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Thereafter, Luciferase assay was conducted to determine the interaction in the NORAD/miR-144-3p/MYCN axis. Besides, its biological function in influencing phenotype changes of renal cancer cells was finally demonstrated by rescue experiments.
    RESULTS: The results manifested that NORAD and MYCN were upregulated, while miR-144-3p was downregulated in renal cancer tissues. Overexpression of NORAD stimulated proliferative and migratory potentials in ACHN and A498 cells, which were partially abolished by co-overexpression of miR-144-3p. Moreover, NORAD/miR-144-3p/MYCN axis was found to be responsible for stimulating the malignant development of renal cancer.
    CONCLUSIONS: LncRNA NORAD stimulates proliferative and migratory potentials in renal cancer by sponging miR-144-3p to upregulate MYCN.
    DOI:  https://doi.org/10.26355/eurrev_202010_23394
  4. Cancer Lett. 2020 Nov 03. pii: S0304-3835(20)30563-2. [Epub ahead of print]
    Bai JY, Jin B, Ma JB, Liu TJ, Yang C, Chong Y, Wang X, He D, Guo P.
      Tumor angiogenesis is a major characteristic of renal cell carcinoma (RCC). Herein, we report a novel mechanism of how lncRNA and androgen receptor (AR) drive the Hedgehog pathway to promote tumor angiogenesis in RCC. We found that the high expression of lncRNA HOTAIR in RCC is associated with poor prognosis. Moreover, HOTAIR and AR form a feedback loop to promote the expression of each other. Interestingly, we also found that in RCC, HOTAIR is associated with the Hedgehog pathway, especially GLI2, via bioinformatics analysis. Furthermore, HOTAIR promotes GLI2 expression in the presence of AR. Mechanistically, HOTAIR interacts with AR and they cooperatively bind to GLI2 promoter and increase its transcription activity. We further confirmed how HOTAIR-AR axis regulates GLI2 expression by analyzing its function in RCC cells and found that HOTAIR and AR synergistically enhanced the expression of GLI2 downstream genes, such as VEGFA, PDGFA, and cancer stem cell transcription factors, and promoted tumor angiogenesis and cancer stemness in RCC cells both in vitro and in tumor xenografts. Overall, these findings suggest that HOTAIR and GLI2 could be novel therapeutic targets against RCC.
    Keywords:  Androgen receptor; Angiogenesis; GLI2; HOTAIR; Renal cell carcinoma
    DOI:  https://doi.org/10.1016/j.canlet.2020.10.031