bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020‒08‒09
seven papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine


  1. Int J Mol Sci. 2020 Aug 05. pii: E5616. [Epub ahead of print]21(16):
    Groeneweg KE, Duijs JMGJ, Florijn BW, van Kooten C, de Fijter JW, van Zonneveld AJ, Reinders MEJ, Bijkerk R.
      Acute rejection (AR) of a kidney graft in renal transplant recipients is associated with microvascular injury in graft dysfunction and, ultimately, graft failure. Circulating long noncoding RNAs (lncRNAs) may be suitable markers for vascular injury in the context of AR. Here, we first investigated the effect of AR after kidney transplantation on local vascular integrity and demonstrated that the capillary density markedly decreased in AR kidney biopsies compared to pre-transplant biopsies. Subsequently, we assessed the circulating levels of four lncRNAs (LNC-RPS24, LNC-EPHA6, MALAT1, and LIPCAR), that were previously demonstrated to associate with vascular injury in a cohort of kidney recipients with a stable kidney transplant function (n = 32) and recipients with AR (n = 15). The latter were followed longitudinally six and 12 months after rejection. We found higher levels of circulating LNC-EPHA6 during rejection, compared with renal recipients with a stable kidney function (p = 0.017), that normalized one year after AR. In addition, LNC-RPS24, LNC-EPHA6, and LIPCAR levels correlated significantly with the vascular injury marker soluble thrombomodulin. We conclude that AR and microvascular injury are associated with higher levels of circulating LNC-EPHA6, which emphasizes the potential role of lncRNAs as biomarker in the context of AR.
    Keywords:  kidney transplantation; long noncoding RNA; microvascular injury; rejection
    DOI:  https://doi.org/10.3390/ijms21165616
  2. Cancer Cell Int. 2020 ;20 338
    Li D, Li C, Chen Y, Teng L, Cao Y, Wang W, Pan H, Xu Y, Yang D.
      Background: Cell autophagy has been proposed to be involved in drug resistance therapy. However, how the long non-coding RNA (lncRNA) reduces risks of drug resistance in renal cancer (RC) cells needs a thorough inquiry. This study was assigned to probe the effect and mechanism of HOTAIR on sunitinib resistance of RC.Methods: Clinical RC tissues and para-carcinoma tissues were obtained to detect the expressions of miR-17-5p, HOTAIR and Beclin1. Sunitinib-resistant cells (786-O-R and ACHN-R) were constructed using parental RC cells (786-O and ACHN). The resistance of 786-O-R and ACHN-R cells to sunitinib was examined. Western blot and qRT-PCR were assayed to obtain the expressions of miR-17-5p, HOTAIR and Beclin1. The effects of HOTAIR knockdown or miR-17-5p overexpression/knockdown on cell autophagy and sunitinib resistance were measured by MDC staining, immunofluorescence and Western blot. The sensitivity of RC cells to sunitinib and change in cell clone formation after sunitinib treatment were assessed by CCK-8 assay and colony formation assay, respectively. The relationships among HOTAIR, miR-17-5p and Beclin1 were verified by dual-luciferase reporter gene and RIP assay. The role of HOTAIR knockdown in sunitinib resistance was verified in nude mice.
    Results: HOTAIR expression in sunitinib-resistant cells is higher than that in parental cells. Knockdown of HOTAIR in sunitinib-resistant cells lead to refrained sunitinib resistance and cell autophagy both in vivo and in vitro. Activation of autophagy could raise resistance to sunitinib in RC cells, while inhibition of autophagy could improve the sensitivity of sunitinib-resistant cells to sunitinib. HOTAIR could compete with miR-17-5p to regulate Beclin1 expression. Knockdown of miR-17-5p in parental cells increases cell resistant to sunitinib, and overexpression of miR-17-5p in sunitinib-resistant cells increases cell sensitive to sunitinib.
    Conclusion: HOTAIR negatively targets miR-17-5p to activate Beclin1-mediated cell autophagy, thereby enhancing sunitinib resistance in RC cells.
    Keywords:  Autophagy; Beclin1; Drug resistance; HOTAIR; LncRNA; Renal cancer; Sunitinib; miR-17-5p
    DOI:  https://doi.org/10.1186/s12935-020-01419-0
  3. Eur Rev Med Pharmacol Sci. 2020 Jul;pii: 22205. [Epub ahead of print]24(14): 7556
    Dong JS, Wu B, Jiang B.
      Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA SNHG7 promotes the proliferation and inhibits apoptosis of renal cell cancer cells by downregulating CDKN1A, by J.-S. Dong, B. Wu, B. Jiang, published in Eur Rev Med Pharmacol Sci 2019; 23 (23): 10241-10247-DOI: 10.26355/eurrev_201912_19661-PMID: 31841178" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19661.
    DOI:  https://doi.org/10.26355/eurrev_202007_22205
  4. Life (Basel). 2020 Aug 01. pii: E131. [Epub ahead of print]10(8):
    Lin J, Jiang Z, Liu C, Zhou D, Song J, Liao Y, Chen J.
      Renal fibrosis is an unavoidable consequence that occurs in nearly all of the nephropathies. It is characterized by a superabundant deposition and accumulation of extracellular matrix (ECM). All compartments in the kidney can be affected, including interstitium, glomeruli, vasculature, and other connective tissue, during the pathogenesis of renal fibrosis. The development of this process eventually causes destruction of renal parenchyma and end-stage renal failure, which is a devastating disease that requires renal replacement therapies. Recently, long non-coding RNAs (lncRNAs) have been emerging as key regulators governing gene expression and affecting various biological processes. These versatile roles include transcriptional regulation, organization of nuclear domains, and the regulation of RNA molecules or proteins. Current evidence proposes the involvement of lncRNAs in the pathologic process of kidney fibrosis. In this review, the biological relevance of lncRNAs in renal fibrosis will be clarified as important novel regulators and potential therapeutic targets. The biology, and subsequently the current understanding, of lncRNAs in renal fibrosis are demonstrated-highlighting the involvement of lncRNAs in kidney cell function, phenotype transition, and vascular damage and rarefaction. Finally, we discuss challenges and future prospects of lncRNAs in diagnostic markers and potential therapeutic targets, hoping to further inspire the management of renal fibrosis.
    Keywords:  fibrosis; gene therapy; long non-coding RNA; myofibroblast; phenotype transition
    DOI:  https://doi.org/10.3390/life10080131
  5. Basic Res Cardiol. 2020 Aug 03. 115(5): 52
    Abbas N, Perbellini F, Thum T.
      Soon after birth, the regenerative capacity of the mammalian heart is lost, cardiomyocytes withdraw from the cell cycle and demonstrate a minimal proliferation rate. Despite improved treatment and reperfusion strategies, the uncompensated cardiomyocyte loss during injury and disease results in cardiac remodeling and subsequent heart failure. The promising field of regenerative medicine aims to restore both the structure and function of damaged tissue through modulation of cellular processes and regulatory mechanisms involved in cardiac cell cycle arrest to boost cardiomyocyte proliferation. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are functional RNA molecules with no protein-coding function that have been reported to engage in cardiac regeneration and repair. In this review, we summarize the current understanding of both the biological functions and molecular mechanisms of ncRNAs involved in cardiomyocyte proliferation. Furthermore, we discuss their impact on the structure and contractile function of the heart in health and disease and their application for therapeutic interventions.
    Keywords:  Cardiomyocyte proliferation; Heart regeneration; MicroRNAs; circRNAs; lncRNAs
    DOI:  https://doi.org/10.1007/s00395-020-0816-0
  6. Diabetes Metab Syndr Obes. 2020 ;13 2477-2483
    Zhang J, Song L, Ma Y, Yin Y, Liu X, Luo X, Sun J, Wang L.
      Background: It has been reported that lncRNA MEG8 can be induced by glucose in mice model of kidney injury, indicating its role in diabetic nephropathy (DN). This study was carried out to explore the role of MEG8 in DN.Materials and Methods: The expression of MEG8 and miR-770-5p in plasma samples from DN patients (n = 66), diabetic patients (DM patients with no complications, n = 66) and healthy controls (n = 66) was detected by RT-qPCR. The interaction between MEG8 and miR-770-5p in podocyte cells was evaluated by transient transfections. Cell apoptosis under high-glucose treatment was detected by cell apoptosis assay.
    Results: MEG8 and miR-770-5p were upregulated in plasma of DM patients and were further upregulated in DN patients. MEG8 was positively correlated with miR-770-5p. In podocyte cells, high-glucose treatment resulted in increased expression levels of MEG8 and miR-770-5p. In podocyte cells, overexpression of MEG8 resulted in upregulated expression of miR-770-5p and decreased methylation of the miR-770-5p gene. Cell apoptosis analysis showed that overexpression of MEG8 and miR-770-5p resulted in increased cell apoptotic rate under glucose treatment. In addition, combined overexpression of MEG8 and miR-770-5p showed stronger effects.
    Conclusion: MEG8 may upregulate miR-770-5p through methylation to promote DN by promoting cell apoptosis.
    Keywords:  MEG8; apoptosis; diabetic nephropathy; miR-770-5p
    DOI:  https://doi.org/10.2147/DMSO.S255183
  7. Brief Bioinform. 2020 Aug 07. pii: bbaa178. [Epub ahead of print]
    Zhang S, He X, Zhang R, Deng W.
      Mounting evidence has shown the involvement of long non-coding RNAs (lncRNAs) during various cancer metastatic events (abbreviated as CMEs, e.g. cancer cell invasion, intravasation, extravasation, proliferation, etc.) that may cooperatively facilitate malignant tumor spread and cause massive patient deaths. The study of lncRNA-CME associations might help understand lncRNA functions in metastasis and present reliable biomarkers for early dissemination detection and optimized treatment. Therefore, we developed a database named 'lncR2metasta' by manually compiling experimentally supported lncRNAs during various CMEs from existing studies. LncR2metasta documents 1238 associations between 304 lncRNAs and 39 CMEs across 54 human cancer subtypes. Each entry of lncR2metasta contains detailed information on a lncRNA-CME association, including lncRNA symbol, a specific CME, brief description of the association, lncRNA category, lncRNA Entrez or Ensembl ID, lncRNA genomic location and strand, lncRNA experiment, lncRNA expression pattern, detection method, target gene (or pathway) of lncRNA, lncRNA regulatory role on a CME, cancer name and the literature reference. An easy-to-use web interface was deployed in lncR2metasta for its users to easily browse, search and download as well as to submit novel lncRNA-CME associations. LncR2metasta will be a useful resource in cancer research community. It is freely available at http://lncR2metasta.wchoda.com.
    Keywords:  biomarker; cancer metastatic event; cancer treatment; database; lncRNA
    DOI:  https://doi.org/10.1093/bib/bbaa178