| First Author | Huang G | Year | 2020 |
| Journal | Carcinogenesis | Volume | 41 |
| Issue | 9 | Pages | 1294-1305 |
| PubMed ID | 31958132 | Mgi Jnum | J:296621 |
| Mgi Id | MGI:6467563 | Doi | 10.1093/carcin/bgz141 |
| Citation | Huang G, et al. (2020) RNA-binding protein CUGBP1 controls the differential INSR splicing in molecular subtypes of breast cancer cells and affects cell aggressiveness. Carcinogenesis 41(9):1294-1305 |
| abstractText | 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. |