bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020‒10‒18
six papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine
  1. lncRNAHIF1A-AS2 Promotes Renal Carcinoma Cell Proliferation and Migration via miR-130a-5p/ERBB2 Pathway.
  2. Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis.
  3. Identification of unique long non-coding RNAs as putative biomarkers for chromophobe renal cell carcinoma.
  4. Identification of candidate lncRNA biomarkers for renal fibrosis: A systematic review.
  5. Circulating Non-coding RNAs in Renal Cell Carcinoma-Pathogenesis and Potential Implications as Clinical Biomarkers.
  6. Identification and characterization of functional long noncoding RNAs in cancer.
  1. Onco Targets Ther. 2020 ;13 9807-9820
    lncRNAHIF1A-AS2 Promotes Renal Carcinoma Cell Proliferation and Migration via miR-130a-5p/ERBB2 Pathway.
    Yunxiao Zhu, Ziyi Yang, Han Chen, Yang Pan, Lifeng Gong, Falin Chen, Xiaoxiang Jin, Shuang Wen, Yi Li, Gang Chen.
      Background: Long non-coding RNAs (lncRNAs) are essential for tumorigenesis and progression of diverse cancers. This study aims to investigate the roles of lncRNAs on renal carcinoma.Methods: The expression of lncRNA HIF1A-AS2 in clear cell renal cell carcinoma (ccRCC) and adjacent non-cancer tissues was identified by quantitative real-time PCR (qRT-PCR). Investigations were performed on biological function of lncRNA HIF1A-AS2 on cell proliferation, cell cycle, apoptosis and invasion of ccRCC by overexpression and knockdown experiments. Further, luciferase reporter assay and Western blot were constructed to explore molecular mechanisms underlying the function of lncRNA HIF1A-AS2.
    Results: HIF1A-AS2 was highly expressed in kidney cancer tissues and ccRCC cells. Interference of HIF1A-AS2 in vivo hindered cell proliferation, invasion and migration while accelerated cell apoptosis. Overexpression of HIF1A-AS2 presented an opposite effect that repressed the expression of miR-130a-5p, and miR-130a-5p inhibited the expression of HIF1A-AS2. Additionally, rescue experiments exhibited that oncogenic function of HIF1A-AS2 was partially dependent on the suppression of miR-130a-5p.
    Conclusion: Our results indicated a critical role for the HIF1A-AS2-miR-130a-5p axis in renal carcinoma progression, which may act as a promising diagnostic biomarker and a pivotal therapeutic target for renal carcinoma cures.
    Keywords:  cell migration; cell proliferation; lncRNA HIF1A-AS2; miR-130a-5p; renal carcinoma cell
    DOI:  https://doi.org/10.2147/OTT.S260191
  2. Cell Transplant. 2020 Jan-Dec;29:29 963689720964413
    Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis.
    Xiaoqiang Zhai, Yan Wu, Zhenlong Wang, Dawei Zhao, Hecheng Li, Tie Chong, Jun Zhao.
      Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.
    Keywords:  Ras-related protein Rab-3D; long noncoding RNA LINC01133; miR-30b-5p; renal cell carcinoma
    DOI:  https://doi.org/10.1177/0963689720964413
  3. Per Med. 2020 Oct 14.
    Identification of unique long non-coding RNAs as putative biomarkers for chromophobe renal cell carcinoma.
    Guanlin Wu, Pengfei Xia, Shixian Yan, Dongming Chen, Lei Xie, Gang Fan.
      Aim: To investigate whether long non-coding RNAs (lncRNAs) can be utilized as molecular biomarkers in predicting the occurrence and progression of chromophobe renal cell carcinoma. Methods & results: Genetic and related clinical traits of chromophobe renal cell carcinoma were downloaded from the Cancer Genome Atlas and used to construct modules using weighted gene coexpression network analysis. In total, 44,889 genes were allocated into 21 coexpression modules depending on intergenic correlation. Among them, the green module was the most significant key module identified by module-trait correlation calculations (R2 = 0.43 and p = 4e-04). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that genes in the green module were enriched in many pathways. Coexpression, protein-protein interaction networks, screening for differentially expressed genes, and survival analysis were used to select hub lncRNAs. Five hub lncRNAs (TTK, CENPE, KIF2C, BUB1, and RAD51AP1) were selected out. Conclusion: Our findings suggest that the five lncRNAs may act as potential biomarkers for chromophobe renal cell carcinoma progression and prognosis.
    Keywords:  The Cancer Genome Atlas; bioinformatics; biomarker; chromophobe renal cell carcinoma; differentially expressed genes; hub gene; long non-coding RNA; weighted gene coexpression network analysis
    DOI:  https://doi.org/10.2217/pme-2020-0020
  4. Life Sci. 2020 Oct 08. pii: S0024-3205(20)31319-9. [Epub ahead of print]262 118566
    Identification of candidate lncRNA biomarkers for renal fibrosis: A systematic review.
    Hongshuai Jia, Tiantian Ma, Chunsheng Hao.
      AIMS: To combine the results of dysregulated lncRNAs in individual renal fibrosis lncRNA expression profiling studies and to identify potential lncRNA biomarkers.MATERIALS AND METHODS: We systematically searched three databases to identify lncRNA expression studies of renal fibrosis in animal models and humans. The lncRNA expression data were extracted from 24 included studies, and a lncRNA vote-counting strategy was applied to identify significant lncRNA biomarkers. The lncLocator algorithm was utilized to predict the potential subcellular localization of these lncRNAs. The predicted targets of the identified lncRNA biomarkers were obtained by searching LncBase v.2 and catRAPID. Finally, GO enrichment and KEGG pathway analyses were performed.
    KEY FINDINGS: We recognized a significant lncRNA signature of 95 differentially expressed lncRNAs in 731 samples from rodent models of renal fibrosis and CKD patients, among which TCONS_01181049 and TCONS_01496394 were commonly upregulated in both urine and renal tissues, while lncRNA-Cancer Susceptibility Candidate 2 was downregulated in both blood and renal tissues. About 73.33% dysregulated lncRNAs in renal fibrosis animal models and 81.82% dysregulated lncRNAs in CKD patients were predicted to be localized to the cytoplasm. The most relevant biological processes and molecular functions associated with these lncRNAs were mRNA processing and RNA binding.
    SIGNIFICANCE: The present systematic review identified 95 significantly dysregulated lncRNAs from 24 studies and future investigations should focus on exploring their potential effects on renal fibrosis and their clinical utility as biomarkers or therapeutic targets.
    Keywords:  Biomarkers; Chronic kidney disease; Renal fibrosis; Systematic review; lncRNA
    DOI:  https://doi.org/10.1016/j.lfs.2020.118566
  5. Front Cell Dev Biol. 2020 ;8 828
    Circulating Non-coding RNAs in Renal Cell Carcinoma-Pathogenesis and Potential Implications as Clinical Biomarkers.
    Dominik A Barth, Rares Drula, Leonie Ott, Linda Fabris, Ondrej Slaby, George A Calin, Martin Pichler.
      Liquid biopsy-the determination of circulating cells, proteins, DNA or RNA from biofluids through a "less invasive" approach-has emerged as a novel approach in all cancer entities. Circulating non-(protein) coding RNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and YRNAs can be passively released by tissue or cell damage or actively secreted as cell-free circulating RNAs, bound to lipoproteins or carried by exosomes. In renal cell carcinoma (RCC), a growing body of evidence suggests circulating non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and YRNAs as promising and easily accessible blood-based biomarkers for the early diagnosis of RCC as well as for the prediction of prognosis and treatment response. In addition, circulating ncRNAs could also play a role in RCC pathogenesis and progression. This review gives an overview over the current study landscape of circulating ncRNAs and their involvement in RCC pathogenesis as well as their potential utility as future biomarkers in RCC diagnosis and treatment.
    Keywords:  biomarker; diagnosis; liquid biopsy; long non-coding RNA; microRNA; prognosis; renal cell carcinoma
    DOI:  https://doi.org/10.3389/fcell.2020.00828
  6. FASEB J. 2020 Oct 15.
    Identification and characterization of functional long noncoding RNAs in cancer.
    Christiane E Olivero, Nadya Dimitrova.
      Long noncoding RNAs (lncRNAs) have emerged as key regulators in a variety of cellular processes that influence disease states. In particular, many lncRNAs are genetically or epigenetically deregulated in cancer. However, whether lncRNA alterations are passengers acquired during cancer progression or can act as tumorigenic drivers is a topic of ongoing investigation. In this review, we examine the current methodologies underlying the identification of cancer-associated lncRNAs and highlight important considerations for evaluating their biological significance as cancer drivers.
    Keywords:  GEMMs; cancer; function; identification; lncRNA
    DOI:  https://doi.org/10.1096/fj.202001951R
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