bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2021‒03‒21
six papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

  1. Front Physiol. 2021 ;12 632398
      Acute kidney injury (AKI) is a severe kidney disease defined by partial or abrupt loss of renal function. Emerging evidence indicates that non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), function as essential regulators in AKI development. Here we aimed to explore the underlying molecular mechanism of the lncRNA H19/miR-130a axis for the regulation of inflammation, proliferation, and apoptosis in kidney epithelial cells. Human renal proximal tubular cells (HK-2) were induced by hypoxia/reoxygenation to replicate the AKI model in vitro. After treatment, the effects of LncRNA H19 and miR-130a on proliferation and apoptosis of HK-2 cells were investigated by CCK-8 and flow cytometry. Meanwhile, the expressions of LncRNA H19, miR-130a, and inflammatory cytokines were detected by qRT-PCR, western blot, and ELISA assays. The results showed that downregulation of LncRNA H19 could promote cell proliferation, inhibit cell apoptosis, and suppress multiple inflammatory cytokine expressions in HK-2 cells by modulating the miR-130a/BCL2L11 pathway. Taken together, our findings indicated that LncRNA H19 and miR-130a might represent novel therapeutic targets and early diagnostic biomarkers for the treatment of AKI.
    Keywords:  BCL2L11; acute kidney injury (AKI); lncRNA H19; miR-130a; renal tubular epithelial cells
  2. J Hematol Oncol. 2021 Mar 19. 14(1): 46
      BACKGROUND: NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood.METHODS: FISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry.
    RESULTS: The expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N6-methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN.
    CONCLUSIONS: TRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.
    Keywords:  M6A modification; NONO-TFE3; PARP1; PTEN; TRAF3IP2-AS1
  3. Cancer Manag Res. 2021 ;13 2287-2294
      Background: Long noncoding RNAs (lncRNAs) have been regarded as crucial regulators in many cancers, including clear cell renal cell carcinoma (ccRCC). This research aimed to explore the biological role and molecular mechanism of lncRNA HCG18 in ccRCC.Materials and Methods: The expression levels of HCG18, miR-152-3p and RAB14 were examined by RT-qPCR. Cell viability, migration and invasion were examined by CCK-8 and transwell assays. Luciferase reporter and RIP assays were adopted to verify the interaction between miR-152-3p and HCG18 or RAB14.
    Results: It was found that HCG18 expression was highly expressed in ccRCC tissues and cells, and patients with high expression of HCG18 had a short overall survival time. Moreover, HCG18 depletion attenuated ccRCC cell viability, migration and invasion. In addition, miR-152-3p was confirmed as a downstream target of HCG18 and was inversely regulated by HCG18, and RAB14 was a target of miR-152-3p. Functional assays demonstrated that miR-152-3p silencing or RAB14 addition abolished the inhibitory effects of HCG18 knockdown on ccRCC progression.
    Conclusion: The results of the present study indicated that HCG18 accelerated the development and progression of ccRCC by upregulating RAB14 via sponging miR-152-3p, suggesting a potential therapeutic target for patients with ccRCC.
    Keywords:  HCG18; RAB14; clear cell renal cell carcinoma; miR-152-3p
  4. Aging (Albany NY). 2021 Mar 10. 13
      Diabetic nephropathy is a lethal disease that can lead to chronic kidney disease and end-stage kidney disease. Exosomes, which are nanosized extracellular vesicles, are closely involved in intercellular communication. Most importantly, exosomes play critical roles in disease occurrence and development. However, the function of exosomes in diabetic nephropathy progression has not been fully elucidated. In the present study, we determined the expression profiles and differences of lncRNAs, mRNAs, circRNAs and miRNAs in exosomes derived from human renal tubular epithelial cells with or without high glucose (HG) treatment. A total of 169 lncRNAs, 885 mRNAs, 3 circRNAs and 152 miRNAs were differentially expressed in exosomes secreted by HG-challenged HK-2 cells (HG group) compared with controls (NC group). The functions of differentially expressed mRNAs, mRNAs colocalized or coexpressed with differentially expressed lncRNAs (DElncRNAs), potential target genes of miRNAs and source genes of circRNAs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. According to these differentially expressed RNAs, we established an integrated circRNA-lncRNA-miRNA-mRNA regulatory network. In conclusion, our study suggested that exosomal lncRNAs, mRNAs, circRNAs and miRNAs participate in the progression of diabetic nephropathy and may be possible biomarkers and therapeutic targets in diabetic nephropathy.
    Keywords:  circRNA; exosome; human renal tubular epithelial cells; lncRNA; miRNA
  5. Cell Biol Int. 2021 Mar 19.
      The immune escape of renal cell carcinoma (RCC) impacts patient survival. However, the molecular mechanism of lncRNA SNHG1 in RCC immune escape remains unclear. Quantitative real-time PCR (qRT-PCR) and western blotting results revealed that the expression of lncRNA SNHG1 and STAT3 were up-regulated in RCC tissues and cells, and that the expression of miR-129-3p was down-regulated. ELISA results revealed the increased levels of immune-related factors (IFN-γ, TNF-α and IL-2) in RCC tissues. SNHG1 knockdown or miR-129-3p overexpression inhibited the proliferation and invasion of A498 and 786-O cells, while the proliferation and cytotoxicity of CD8+ T cells increased, which promoted the secretion of immune-related factors. STAT3 overexpression decreased the protective effect of miR-129-3p overexpression on RCC cell immune escape. In addition, miR-129-3p knockdown and STAT3 overexpression decreased the protective effect of lncRNA SNHG1 knockdown on RCC cell immune escape. In addition, PD-L1 expression was down-regulated after lncRNA SNHG1 knockdown but up-regulated after miR-129-3p knockdown and STAT3 overexpression. Dual-luciferase assays showed that lncRNA SNHG1 targets miR-129-3p, and miR-129-3p targets STAT3. RNA pull-down, RIP assays verified the regulatory relationship between SNHG1 and STAT3. In vivo, shSNHG1 prolonged the overall survival of RCC tumour model mice and inhibited RCC tumour growth and immune escape but increased of CD8+ T cell infiltration in mice. Our findings provide an experimental basis for elucidating the molecular mechanisms of immune escape by RCC and reveal a novel target to treat this disease. This article is protected by copyright. All rights reserved.
    Keywords:  PD-L1; RCC; SNHG1; STAT3; immune escape; miR-129-3p
  6. Front Oncol. 2021 ;11 641343
      Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
    Keywords:  cancer metastasis; colorectal cancer; lncRNAs; markers; signaling pathways; therapy