For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
12
views
24
references
 Top references
cited by
72
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      709
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      LncRNA GATA3‐AS1 facilitates tumour progression and immune escape in triple‐negative breast cancer through destabilization of GATA3 but stabilization of PD‐L1

      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

          Objectives

          Long non‐coding RNAs (lncRNAs) have been demonstrated as crucial regulators in cancer, but whether they are involved in the immune response of cancer cells remains largely undiscovered. GATA3‐AS1 is a novel lncRNA that was upregulated in breast cancer (BC) according to online databases. However, its role in triple‐negative breast cancer (TNBC) was elusive.

          Methods

          GATA3‐AS1 expression in BC tissues and adjacent normal tissues was obtained from online databases. Loss‐of‐function assays were designed and conducted to verify the functional role of GATA3‐AS1 in TNBC cells. Bioinformatic analysis and mechanism experiments were applied to explore the downstream molecular mechanism of GATA3‐AS1. Similarly, the upstream mechanism which led to the upregulation of GATA3‐AS1 in TNBC cells was also investigated.

          Results

          GATA3‐AS1 was markedly overexpressed in TNBC tissues and cells. Knockdown of GATA3‐AS1 suppressed TNBC cell growth and enhanced the resistance of TNBC cells to immune response. GATA3‐AS1 induced the deubiquitination of PD‐L1 through miR‐676‐3p/COPS5 axis. GATA3‐AS1 destabilized GATA3 protein by promoting GATA3 ubiquitination.

          Conclusion

          GATA3‐AS1 contributed to TNBC progression and immune evasion through stabilizing PD‐L1 protein and degrading GATA3 protein, offering a new target for the treatment of TNBC.

          Related collections

          Most cited references24

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

          Deubiquitination and Stabilization of PD-L1 by CSN5.

          Seung-Oe Lim, Chia-Wei Li, Weiya Xia … (2016)
          Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
          Article 0 comments Cited 341 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer

            Katarzyna Augoff, Brian McCue, Edward F. Plow … (2012)
            Background microRNAs have been established as powerful regulators of gene expression in normal physiological as well as in pathological conditions, including cancer progression and metastasis. Recent studies have demonstrated a key role of miR-31 in the progression and metastasis of breast cancer. Downregulation of miR-31 enhances several steps of the invasion-metastasis cascade in breast cancer, i.e., local invasion, extravasation and survival in the circulation system, and metastatic colonization of distant sites. miR-31 exerts its metastasis-suppressor activity by targeting a cohort of pro-metastatic genes, including RhoA and WAVE3. The molecular mechanisms that lead to the loss of miR-31 and the activation of its pro-metastatic target genes during these specific steps of the invasion-metastasis cascade are however unknown. Results In the present report, we identify promoter hypermethylation as one of the major mechanisms for silencing miR-31 in breast cancer, and in the triple-negative breast cancer (TNBC) cell lines of basal subtype, in particular. miR-31 maps to the intronic sequence of a novel long non-coding (lnc)RNA, LOC554202 and the regulation of its transcriptional activity is under control of LOC554202. Both miR-31 and the host gene LOC554202 are down-regulated in the TNBC cell lines of basal subtype and over-expressed in the luminal counterparts. Treatment of the TNBC cell lines with either a de-methylating agent alone or in combination with a de-acetylating agent resulted in a significant increase of both miR-31 and its host gene, suggesting an epigenetic mechanism for the silencing of these two genes by promoter hypermethylation. Finally, both methylation-specific PCR and sequencing of bisulfite-converted DNA demonstrated that the LOC554202 promoter-associated CpG island is heavily methylated in the TNBC cell lines and hypomethylated in the luminal subtypes. Conclusion Loss of miR-31 expression in TNBC cell lines is attributed to hypermethylation of its promoter-associated CpG island. Together, our results provide the initial evidence for a mechanism by which miR-31, an important determinant of the invasion metastasis cascade, is regulated in breast cancer.
            Article 0 comments Cited 175 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression

              Haihai Liang, Tong Yu, Yue Han … (2018)
              Background Ovarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world. The majority of OvCa is diagnosed with metastasis in the abdominal cavity. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor cell metastasis. However, it is still unclear whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell invasion and metastasis in OvCa. Results In this study, using bioinformatcis analysis, we constructed a lncRNA-mediated competing endogenous RNA (ceRNA) network for mesenchymal OvCa and identified lncRNA AP000695.4, which we named pro-transition associated RNA (PTAR). PTAR was significantly up-regulated in the mesenchymal subtype samples compared with the epithelial subtype samples from the TCGA OvCa data sets. In addition, our study showed that PTAR expression was positively correlated with the expression level of ZEB1 in the mesenchymal OvCa samples. Meanwhile, we found that silencing miR-101 promoted cell migration, whereas the overexpression of miR-101 suppressed EMT and cell migration in OvCa cell lines through the regulation of ZEB1. Further analysis showed that enhanced expression of PTAR promoted EMT and metastasis through the regulation of miR-101, whereas silencing PTAR led to the attenuation of TGF-β1-induced tumorigenicity in ovarian cancer cells. Mechanistically, we found that PTAR acted as a ceRNA of miR-101, as forced expression of PTAR reduced the expression and activity of miR-101. More importantly, the knockdown of PTAR reduced tumorigenicity and metastasis in vivo. Conclusions Taken together, the results from our study highlight a role for the PTAR-miR-101-ZEB1 axis in OvCa, which offers novel strategies for the prevention of metastasis in OvCa.
              Article 0 comments Cited 170 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Zhigao Li:
                ORCID: https://orcid.org/0000-0002-4169-143X
                gaozhi216420813@163.com
                Jinsong Wang: jinsou007926454@163.com
                Journal
                Journal ID (nlm-ta): Cell Prolif
                Journal ID (iso-abbrev): Cell Prolif
                Journal ID (doi): 10.1111/(ISSN)1365-2184
                Journal ID (publisher-id): CPR
                Title: Cell Proliferation
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0960-7722
                ISSN (Electronic): 1365-2184
                Publication date (Electronic): 20 July 2020
                Publication date Collection: September 2020
                Volume: 53
                Issue: 9 ( doiID: 10.1111/cpr.v53.9 )
                Electronic Location Identifier: e12855
                Affiliations
                [ 1 ] Department of Breast Surgery Harbin Medical University Cancer Hospital Harbin China
                [ 2 ] Department of Internal Neurology The First Hospital of Suihua City Suihua China
                [ 3 ] Department of Orthopedics People's Hospital of Zhangqiu Jinan China
                Author notes
                [*] [* ] Correspondence

                Zhigao Li and Jinsong Wang, Department of Breast Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, Heilongjiang, China.

                Emails: drzhigaoli@ 123456126.com (ZL), jinsou007926454@ 123456163.com (JW)

                Author information
                https://orcid.org/0000-0002-4169-143X
                Article
                Publisher ID: CPR12855
                DOI: 10.1111/cpr.12855
                PMC ID: 7507373
                PubMed ID: 32687248
                SO-VID: 27fba5d7-8e73-4f85-a620-f47a0f34a5a5
                Copyright © © 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 08 December 2019
                Date revision received : 27 April 2020
                Date accepted : 16 May 2020
                Page count
                Figures: 8, Tables: 0, Pages: 13, Words: 5319
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date September 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:22.09.2020

                ScienceOpen disciplines: Cell biology
                Keywords: cops5,gata3‐as1,immune escape,pd‐l1,triple‐negative breast cancer
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: cops5, gata3‐as1, immune escape, pd‐l1, triple‐negative breast cancer

                Comments

                Comment on this article

                scite_

                Similar content709

                See all similar

                Cited by71

                See all cited by