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RNA-binding protein CUGBP1 controls the differential INSR splicing in molecular subtypes of breast cancer cells and affects cell aggressiveness.

Authors
  • Huang, Gena1, 2, 3, 4
  • Song, Chen2
  • Wang, Ning1, 3, 4
  • Qin, Tao5
  • Sui, Silei6
  • Obr, Alison7
  • Zeng, Li1, 3
  • Wood, Teresa L7
  • Leroith, Derek8
  • Li, Man2
  • Wu, Yingjie1, 3, 4, 8, 9
  • 1 Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 2 Department of Breast Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 3 National Center of Genetically Engineered Animal Models for International Research, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 4 Liaoning Provence Key Lab of Genome Engineered Animal Models, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 5 Department of Pathology, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 6 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 7 Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, NJ, USA. , (Jersey)
  • 8 Division of Endocrinology, Diabetes and Bone Disease, Department of Medicine, Icahn Mount Sinai School of Medicine, New York, NY, USA.
  • 9 College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China. , (China)
Type
Published Article
Journal
Carcinogenesis
Publisher
Oxford University Press
Publication Date
Sep 24, 2020
Volume
41
Issue
9
Pages
1294–1305
Identifiers
DOI: 10.1093/carcin/bgz141
PMID: 31958132
Source
Medline
Language
English
License
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]

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