For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
21
views
29
references
 Top references
cited by
34
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      436
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      SRSF10-mediated IL1RAP alternative splicing regulates cervical cancer oncogenesis via mIL1RAP-NF-κB-CD47 axis

      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

          High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an “accomplice” of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation. SRSF10 modulates the alternate terminator of interleukin-1 receptor accessory protein exon 13 to increase production of the membrane form of interleukin-1 receptor accessory protein. SRSF10-mediated mIL1RAP upregulates the expression of the “don’t eat me” signal CD47 to inhibit macrophage phagocytosis by promoting nuclear factor-κB activation, which is pivotal in inflammatory, immune, and tumorigenesis processes. Altogether, these data reveal a close relationship among HPV infection, alternative splicing and tumor immune evasion, and also suggests that the SRSF10-mIL1RAP-CD47 axis could be an attractive therapeutic target for the treatment of cervical cancer.

          Related collections

          Most cited references29

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

          Alternative splicing and evolution: diversification, exon definition and function.

          Hadas Keren, Galit Lev-Maor, Gil Ast (2010)
          Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals. Splicing can be found in species from bacteria to humans, but its prevalence and characteristics vary considerably. Evolutionary studies are helping to address questions that are fundamental to understanding this important process: how and when did AS evolve? Which AS events are functional? What are the evolutionary forces that shaped, and continue to shape, AS? And what determines whether an exon is spliced in a constitutive or alternative manner? In this Review, we summarize the current knowledge of AS and evolution and provide insights into some of these unresolved questions.
          Article 0 comments Cited 380 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The spliceosome is a therapeutic vulnerability in MYC-driven cancer

            Tiffany Y-T Hsu, Lukas M Simon, Nicholas J Neill … (2015)
            c-MYC (MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. MYC is a transcription factor, and many of its pro-tumorigenic functions have been attributed to its ability to regulate gene expression programs 1–3 . Notably, oncogenic MYC activation has also been shown to increase total RNA and protein production in many tissue and disease contexts 4–7 . While such increases in RNA and protein production may endow cancer cells with pro-tumor hallmarks, this elevation in synthesis may also generate new or heightened burden on MYC-driven cancer cells to properly process these macromolecules 8 . Herein, we discover the spliceosome as a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene, and demonstrate that BUD31 is a component of the core spliceosome required for its assembly and catalytic activity. Core spliceosomal factors (SF3B1, U2AF1, and others) associated with BUD31 are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total pre-mRNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Importantly, genetic or pharmacologic inhibition of the spliceosome in vivo impairs survival, tumorigenicity, and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers.
            Article 0 comments Cited 216 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cancer-associated regulation of alternative splicing.

              Philippe Thibault, Mathieu Durand, Julien Gervais … (2009)
              Alternative splicing of pre-mRNA increases the diversity of protein functions. Here we show that about half of all active alternative splicing events in ovarian and breast tissues are changed in tumors, and many seem to be regulated by a single factor; sequence analysis revealed binding sites for the RNA binding protein FOX2 downstream of one-third of the exons skipped in cancer. High-resolution analysis of FOX2 binding sites defined the precise positions relative to alternative exons at which the protein may function as either a silencer or an enhancer. Most of the identified targets were shifted in the same direction by FOX2 depletion in cell lines as they were in breast and ovarian cancer tissues. Notably, we found expression of FOX2 itself is downregulated in ovarian cancer and its splicing is altered in breast cancer samples. These results suggest that the decreased expression of FOX2 in cancer tissues modulates splicing and controls proliferation.
              Article 0 comments Cited 138 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Zhigang Zhang: +86-21-34206763 , zzhang@shsci.org
                Yincheng Teng: +86-13816398069 , ycteng@sjtu.edu.cn
                Journal
                Journal ID (nlm-ta): Oncogene
                Journal ID (iso-abbrev): Oncogene
                Title: Oncogene
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 0950-9232
                ISSN (Electronic): 1476-5594
                Publication date (Electronic): 12 February 2018
                Publication date PMC-release: 12 February 2018
                Publication date (Print): 2018
                Volume: 37
                Issue: 18
                Pages: 2394-2409
                Affiliations
                [1 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, , Shanghai Jiao Tong University School of medicine, ; Shanghai, China
                [2 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, , Central South University, ; Changsha, China
                [3 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, , Shanghai Jiao Tong University, ; Shanghai, China
                [4 ]ISNI 0000 0004 1799 0784, GRID grid.412676.0, Department of Orthopedics, , The First Affiliated Hospital of Nanjing Medical University, ; Nanjing, China
                Article
                Publisher ID: 119
                DOI: 10.1038/s41388-017-0119-6
                PMC ID: 5931977
                PubMed ID: 29429992
                SO-VID: c64cb68a-b796-4d93-9314-78043d28dfba
                Copyright © © The Author(s) 2018
                License:

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.

                History
                Date received : 26 September 2017
                Date revision received : 6 December 2017
                Date accepted : 14 December 2017
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Macmillan Publishers Limited, part of Springer Nature 2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

                Comments

                Comment on this article

                scite_

                Similar content436

                See all similar

                Cited by45

                See all cited by

                Most referenced authors871

                See all reference authors