RNA-binding protein CUGBP1 controls the differential INSR splicing in molecular subtypes of breast cancer cells and affects cell aggressiveness.
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Authors
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Huang, Gena1, 2, 3, 4
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Song, Chen2
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Wang, Ning1, 3, 4
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Qin, Tao5
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Sui, Silei6
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Obr, Alison7
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Zeng, Li1, 3
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Wood, Teresa L7
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Leroith, Derek8
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Li, Man2
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Wu, Yingjie1, 3, 4, 8, 9
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1
Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, Liaoning, China.
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(China)
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2
Department of Breast Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
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(China)
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3
National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, Liaoning, China.
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(China)
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4
Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, Liaoning, China.
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(China)
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5
Department of Pathology, Dalian Medical University, Dalian, Liaoning, China.
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(China)
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6
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
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(China)
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7
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, NJ, USA.
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(Jersey)
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8
Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn Mount Sinai School of Medicine, New York, NY, USA.
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9
College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China.
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(China)
- Type
- Published Article
- Journal
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Carcinogenesis
- Publisher
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Oxford University Press
- Publication Date
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Sep 24, 2020
- Volume
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41
- Issue
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9
- Pages
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1294–1305
- Identifiers
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DOI: 10.1093/carcin/bgz141
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PMID: 31958132
- Source
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Medline
- Language
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English
- License
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Unknown
Abstract
The insulin receptor gene (INSR) undergoes alternative splicing to give rise to two functionally related, but also distinct, isoforms IR-A and IR-B, which dictate proliferative and metabolic regulations, respectively. Previous studies identified the RNA-binding protein CUGBP1 as a key regulator of INSR splicing. In this study, we show that the differential splicing of INSR occurs more frequently in breast cancer than in non-tumor breast tissues. In breast cancer cell lines, the IR-A:IR-B ratio varies in different molecular subtypes, knockdown or overexpression of CUGBP1 gene in breast cancer cells altered IR-A:IR-B ratio through modulation of IR-A expression, thereby reversed or enhanced the insulin-induced oncogenic behavior of breast cancer cells, respectively. Our data revealed the predominant mitogenic role of IR-A isoform in breast cancer and depicted a novel interplay between INSR and CUGBP1, implicating CUGBP1 and IR-A isoform as the potential therapeutic targets and biomarkers for breast cancer. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 10/06/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/31958132
