For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
39
references
 Top references
cited by
5
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      516
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: The current studies only indicated that long non-coding RNA (lncRNA) APCDD1L-AS1, as a novel lncRNA, may play a role in oral squamous cell carcinoma and lung cancer. However, its potential role in clear cell renal cell carcinoma (ccRCC) and its possible mechanism of action remain vague.

          Methods: TCGA-KIRC and GEO data and qRT-PCR and pyrosequencing results of clinical specimens were used to identify the expression level and DNA methylation status of APCDD1L-AS1. The effects of APCDD1L-AS1 overexpression on ccRCC growth and metastasis were determined by function experiments. Western blot and Tandem mass tags (TMT) were utilized to explore the relationship between APCDD1L-AS1 and VHL expression and its downstream underlying mechanisms.

          Results: The expression of APCDD1L-AS1 was downregulated in ccRCC. Decreased APCDD1L-AS1 expression was related to higher tumor stage and histological grade and shorter RFS (Relapse-free survival). Besides, APCDD1L-AS1 overexpression restrained the growth and metastasis of ccRCC cells in vitro and in vivo. Moreover, reduced APCDD1L-AS1 expression could be caused by DNA hypermethylation and loss of von Hippel Lindau (VHL) protein expression. Furthermore, the dysregulation of histones expression caused by APCDD1L-AS1 overexpression may be one of the important mechanisms to suppress the progression of ccRCC.

          Conclusion: APCDD1L-AS1 was able to inhibit the progression of ccRCC, and its decreased expression could be caused by DNA hypermethylation and loss of VHL protein expression. Therefore, APCDD1L-AS1 may serve as a new therapeutic target in the treatment of ccRCC.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

          Jacques Ferlay, Hai-Rim Shin, Freddie Bray … (2010)
          Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed. Copyright © 2010 UICC.
          Article 0 comments Cited 1019 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.

            Jeremy Schwartzentruber, Andrey Korshunov, Xiao-Yang Liu … (2012)
            Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
            Article 0 comments Cited 428 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.

              P H Maxwell, M S Wiesener, G W Chang … (1999)
              Hypoxia-inducible factor-1 (HIF-1) has a key role in cellular responses to hypoxia, including the regulation of genes involved in energy metabolism, angiogenesis and apoptosis. The alpha subunits of HIF are rapidly degraded by the proteasome under normal conditions, but are stabilized by hypoxia. Cobaltous ions or iron chelators mimic hypoxia, indicating that the stimuli may interact through effects on a ferroprotein oxygen sensor. Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation. In VHL-defective cells, HIF alpha-subunits are constitutively stabilized and HIF-1 is activated. Re-expression of pVHL restored oxygen-dependent instability. pVHL and HIF alpha-subunits co-immunoprecipitate, and pVHL is present in the hypoxic HIF-1 DNA-binding complex. In cells exposed to iron chelation or cobaltous ions, HIF-1 is dissociated from pVHL. These findings indicate that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF alpha-subunits. Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing.
              Article 0 comments Cited 396 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Biol Sci
                Journal ID (iso-abbrev): Int J Biol Sci
                Journal ID (publisher-id): ijbs
                Title: International Journal of Biological Sciences
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1449-2288
                Publication date Collection: 2022
                Publication date (Electronic): 21 March 2022
                Volume: 18
                Issue: 6
                Pages: 2583-2596
                Affiliations
                [1 ]Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.
                [2 ]Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.
                [3 ]Institute of Urology, Peking University, Beijing 100034, P.R. China.
                Author notes
                ✉ Corresponding authors: Dr. Yanqing Gong, E-mail: yqgong@ 123456bjmu.edu.cn ; Mailing address: No. 8, Xishiku Street, Xicheng District, Beijing 100034, China. Dr. Kan Gong, E-mail: gongkan_pku@ 123456126.com ; Mailing address: No. 8, Xishiku Street, Xicheng District, Beijing 100034, China; Tel: +86-010-83575101; Fax: +86-010-66551122.

                *These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: ijbsv18p2583
                DOI: 10.7150/ijbs.71519
                PMC ID: 8990466
                PubMed ID: 35414787
                SO-VID: a2dcc92c-8b1c-4ee0-a4b8-c7a3e4a393b1
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 28 January 2022
                Date accepted : 5 March 2022
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Life sciences
                Keywords: long non-coding rna,apcdd1l-as1,clear cell renal cell carcinoma,dna hypermethylation,von hippel lindau
                Data availability:
                ScienceOpen disciplines: Life sciences
                Keywords: long non-coding rna, apcdd1l-as1, clear cell renal cell carcinoma, dna hypermethylation, von hippel lindau

                Comments

                Comment on this article

                scite_

                Similar content516

                See all similar

                Cited by5

                See all cited by

                Most referenced authors624

                See all reference authors