bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020–07–12
seven papers selected by
Nikita Dewani, Max Delbrück Centre for Molecular Medicine
  1. LINC00707 accelerates the proliferation, migration and invasion of clear cell renal cell carcinoma.
  2. LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1.
  3. Inhibition of lncRNA-PAX8-AS1-N directly associated with VEGF/TGF-β1/8-OhdG enhances podocyte apoptosis in diabetic nephropathy.
  4. Proximal Tubular Transcription Factors in Acute Kidney Injury: Recent Advances.
  5. Long non-coding RNA TINCR as potential biomarker and therapeutic target for cancer.
  6. Predicting microRNA-disease associations from lncRNA-microRNA interactions via Multiview Multitask Learning.
  7. Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma.
  1. Eur Rev Med Pharmacol Sci. 2020 Jun;pii: 21647. [Epub ahead of print]24(12): 6616-6622
    LINC00707 accelerates the proliferation, migration and invasion of clear cell renal cell carcinoma.
    L-R Pang, M-X Huang, H Li, G Chen, G-P Zhong, B Yao, J Chen.
       OBJECTIVE: Long noncoding RNAs (lncRNAs) have been well concerned in tumor researches, which are believed to influence tumorigenesis and tumor progression. This study aims to uncover the role of LINC00707 in clear cell renal cell carcinoma (ccRCC) and the underlying mechanism.
    MATERIALS AND METHODS: Differentially expressed lncRNAs in ccRCC tissues and renal epithelial tissues were analyzed in The Cancer Genome Atlas (TCGA), and LINC00707 was screened out. Expression level of LINC00707 in ccRCC cell lines was determined as well. Regulatory effects of LINC00707 on influencing proliferative, migratory, and invasive abilities of 786-O and 769-P cells were assessed. At last, relative levels of epithelial-mesenchymal transition (EMT)-related genes E-cadherin and N-cadherin in 786-O and 769-P cells were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and Western blot.
    RESULTS: LINC00707 was upregulated in ccRCC tissues and cell lines. Silence of LINC00707 attenuated proliferative, migratory, and invasive abilities of 786-O and 769-P cells. Moreover, knockdown of LINC00707 upregulated E-cadherin and downregulated N-cadherin in ccRCC cells at both mRNA and protein levels.
    CONCLUSIONS: LINC00707 is upregulated in ccRCC, which could promote cancer cells to proliferate, migrate, and invade. LINC00707 accelerates the progression of ccRCC by activating EMT pathway.
    DOI:  https://doi.org/10.26355/eurrev_202006_21647
  2. Cell Cycle. 2020 Jul 05. 1-10
    LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1.
    Feng Guo, Weimin Wang, Yi Song, Lina Wu, Jiao Wang, Yanyan Zhao, Xiaojun Ma, Hongfei Ji, Yanling Liu, Zhizhen Li, Guijun Qin.
      LncRNAs play important roles in the regulation of podocyte apoptosis in diabetic nephropathy (DN). However, the role of lncRNA SNHG17 in controlling mitophagy-induced apoptosis of podocytes in DN is unknown. This study aims to elucidate the underlying mechanism of lncRNA SNHG17 in the regulation of mitophagy-induced apoptosis of podocytes in DN. LncRNA SNHG17 and Mammalian Sterile 20-like kinase 1 (Mst1) expression were upregulated in glomeruli and podocytes of DM mice and high glucose-treated podocytes, whereas Parkin expression was downregulated. LncRNA SNHG17 overexpression suppressed mitophagy and induced apoptosis of podocytes while silencing lncRNA SNHG17 promoted mitophagy and reduced the apoptosis of podocytes. In addition, lncRNA SNHG17 interacted with Mst1 and regulated the degradation of Mst1. We further found lncRNA SNHG17 regulated Parkin expression through Mst1. Mechanistically, lncRNA SNHG17 regulated Parkin-dependent mitophagy and apoptosis of podocytes through regulating Mst1. Finally, silencing lncRNA SNHG17 promoted mitophagy and relieved DNin vivo. In conclusion, lncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through regulating the degradation of Mst1.
    Keywords:  Mst1; Parkin; apoptosis; diabetic nephropathy; lncRNA SNHG17; mitophagy
    DOI:  https://doi.org/10.1080/15384101.2020.1783481
  3. Eur Rev Med Pharmacol Sci. 2020 Jun;pii: 21676. [Epub ahead of print]24(12): 6864-6872
    Inhibition of lncRNA-PAX8-AS1-N directly associated with VEGF/TGF-β1/8-OhdG enhances podocyte apoptosis in diabetic nephropathy.
    Y Shen, Z-W Tong, Y Zhou, Y Sun, Y Xie, R Li, H Liu.
       OBJECTIVE: Diabetic nephropathy (DN), the microvascular complications of diabetes, is one of the world's public health hazard. But the detailed mechanism of the occurrence and development remains unclear. Oxidative stress caused by multiple factors is recognized as the main cause of disease, and it is also a research focus. Recently, long non-coding RNAs (lncRNAs) have been declared to involve in a large of important bioactivities in many different diseases. In our study, we aimed to verify whether lncRNA PAX8-AS1-N involved in protecting podocyte apoptosis and directly associated with VEGF/TGF-β1/8-OhdG levels in DN, and further investigated the detailed mechanism that PAX8-AS1-N regulated the pathological process.
    MATERIALS AND METHODS: We used blood and urine samples of DN patients to detect the expression of lncRNA-PAX8-AS1-N and VEGF/TGF-β1/8-OhdG by ELISA and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Albuminuria level, relative PAX8-AS1-N and VEGF/TGF-β1/8-OhdG levels, and VEGF/TGF-β1/8-OhdG and cleaved-caspase-3 protein levels were detected by ELISA, qRT-PCR, and Western blot, respectively. CCK8 assay was used to measure the proliferation ability of conditionally immortalized mouse podocytes (MPC5). And we used the TUNEL assay to detect MPC5 apoptosis. Luciferase reporter assay was used to confirm the direct target of PAX8-AS-N and miR-17-5p in MPC5.
    RESULTS: We found that the lncRNA PAX8-AS1-N was lowly expressed and high expression of VEGF/TGF-β1/8-OhdG and high level of albuminuria in DN patients and high-glucose-treated MPC5. Besides, we proved that LV-PAX8-AS1-N decreased MPC5 apoptosis and suppressed the expression of VEGF/TGF-β1/8-OhdG in vitro experiment. At last, the overexpression of miR-17-5p markedly induced cell apoptosis in MPC5 with high glucose (HG) model. STAT3 reverses the effects of miR-17-5p overexpression in MPC5 with HG model.
    CONCLUSIONS: Above that, we found that lncRNA PAX8-AS1-N/miR-17-5p/STAT3 axis was closely related the progression of DN, which could be a potential target for treating DN patients.
    DOI:  https://doi.org/10.26355/eurrev_202006_21676
  4. Nephron. 2020 Jul 09. 1-3
    Proximal Tubular Transcription Factors in Acute Kidney Injury: Recent Advances.
    Sian E Piret, Sandeep K Mallipattu.
      The proximal tubule (PT) is a major target in acute kidney injury (AKI), leading to profound changes in PT cell biology. Amongst the genes with early and robust changes in expression are many transcription factors (TFs), which themselves account for other transcriptomic changes. Potentially important TFs are being revealed in large sequencing datasets; however, to understand whether these TFs account for adaptive or maladaptive changes requires further mechanistic studies, which may reveal novel therapeutic targets. This mini review will highlight the identification and biology of 3 novel TFs in AKI: Sox9, Foxm1, and Foxo3.
    Keywords:  Acute kidney injury; Proximal tubule; RNA sequencing; Transcription factors
    DOI:  https://doi.org/10.1159/000508856
  5. Life Sci. 2020 Jul 02. pii: S0024-3205(20)30785-2. [Epub ahead of print] 118035
    Long non-coding RNA TINCR as potential biomarker and therapeutic target for cancer.
    Uttam Sharma, Tushar Singh Barwal, Akshay Malhotra, Neha Pant, Vivek, Damayanti Dey, Ashima Gautam, Hardeep Singh Tuli, Karen M Vasquez, Aklank Jain.
      Despite the recent scientific advances made in cancer diagnostics and therapeutics, cancer still remains the second leading cause of death worldwide. Thus, there is a need to identify new potential biomarkers/molecular targets to improve the diagnosis and treatment of cancer patients. In this regard, long non-coding RNAs (lncRNAs), a type of non-coding RNA molecule, have been found to play important roles in diverse biological processes, including tumorigenesis, and may provide new biomarkers and/or molecular targets for the improved detection of treatment of cancer. For example, one lncRNA, tissue differentiation-inducing non-protein coding RNA (TINCR) has been found to be significantly dysregulated in many cancers, and has an impact on tumor development and progression through targeting pivotal molecules in cancer-associated signaling pathways. Hence, based on recent discoveries, herein, we discuss the regulatory functions and the underlying mechanisms of how TINCR regulates signaling pathways attributed to cancer hallmarks associated with the pathogenesis of various human cancers. We also highlight studies assessing its potential clinical utility as a biomarker/target for early detection, cancer risk stratification, and personalized cancer therapies.
    Keywords:  Biomarker; Cancer; LncRNA; Long non-coding RNA; TINCR; Tissue differentiation-inducing non-protein coding RNA
    DOI:  https://doi.org/10.1016/j.lfs.2020.118035
  6. Brief Bioinform. 2020 Jul 07. pii: bbaa133. [Epub ahead of print]
    Predicting microRNA-disease associations from lncRNA-microRNA interactions via Multiview Multitask Learning.
    Yu-An Huang, Keith C C Chan, Zhu-Hong You, Pengwei Hu, Lei Wang, Zhi-An Huang.
       MOTIVATION: Identifying microRNAs that are associated with different diseases as biomarkers is a problem of great medical significance. Existing computational methods for uncovering such microRNA-diseases associations (MDAs) are mostly developed under the assumption that similar microRNAs tend to associate with similar diseases. Since such an assumption is not always valid, these methods may not always be applicable to all kinds of MDAs. Considering that the relationship between long noncoding RNA (lncRNA) and different diseases and the co-regulation relationships between the biological functions of lncRNA and microRNA have been established, we propose here a multiview multitask method to make use of the known lncRNA-microRNA interaction to predict MDAs on a large scale. The investigation is performed in the absence of complete information of microRNAs and any similarity measurement for it and to the best knowledge, the work represents the first ever attempt to discover MDAs based on lncRNA-microRNA interactions.
    RESULTS: In this paper, we propose to develop a deep learning model called MVMTMDA that can create a multiview representation of microRNAs. The model is trained based on an end-to-end multitasking approach to machine learning so that, based on it, missing data in the side information can be determined automatically. Experimental results show that the proposed model yields an average area under ROC curve of 0.8410+/-0.018, 0.8512+/-0.012 and 0.8521+/-0.008 when k is set to 2, 5 and 10, respectively. In addition, we also propose here a statistical approach to predicting lncRNA-disease associations based on these associations and the MDA discovered using MVMTMDA.
    AVAILABILITY: Python code and the datasets used in our studies are made available at https://github.com/yahuang1991polyu/MVMTMDA/.
    Keywords:  lncRNA–microRNA interaction; microRNA-disease association; multiview multitask learning
    DOI:  https://doi.org/10.1093/bib/bbaa133
  7. Cell Death Dis. 2020 Jul 08. 11(7): 515
    Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma.
    Yuenan Liu, Gong Cheng, Ziwei Huang, Lin Bao, Jingchong Liu, Cheng Wang, Zhiyong Xiong, Lijie Zhou, Tianbo Xu, Di Liu, Hongmei Yang, Ke Chen, Xiaoping Zhang.
      Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC.
    DOI:  https://doi.org/10.1038/s41419-020-2713-8
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