MYC Regulates α6 Integrin Subunit Expression and Splicing Under Its Pro-Proliferative ITGA6A Form in Colorectal Cancer Cells
| العنوان: | MYC Regulates α6 Integrin Subunit Expression and Splicing Under Its Pro-Proliferative ITGA6A Form in Colorectal Cancer Cells |
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| المؤلفون: | Salah Boudjadi, Jean-François Groulx, Jean-François Beaulieu |
| المصدر: | Cancers, Vol 10, Iss 2, p 42 (2018) Cancers Cancers; Volume 10; Issue 2; Pages: 42 |
| بيانات النشر: | MDPI AG, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Regulation of gene expression, Cancer Research, Gene knockdown, Messenger RNA, colorectal cancer, MYC, integrin α6β4, ITGA6, alternative splicing, ESRP2, Alternative splicing, Biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article, Small hairpin RNA, 03 medical and health sciences, Splicing factor, 030104 developmental biology, Oncology, RNA splicing, Cancer research |
| الوصف: | The α6 integrin subunit (ITGA6) pre-mRNA undergoes alternative splicing to form two splicing variants, named ITGA6A and ITGA6B. In primary human colorectal cancer cells, the levels of both ITGA6 and β4 integrin subunit (ITGB4) subunits of the α6β4 integrin are increased. We previously found that the upregulation of ITGA6 is a direct consequence of the increase of the pro-proliferative ITGA6A variant. However, the mechanisms that control ITGA6 expression and splicing into the ITGA6A variant over ITGA6B in colorectal cancer cells remain poorly understood. Here, we show that the promoter activity of the ITGA6 gene is regulated by MYC. Pharmacological inhibition of MYC activity with the MYC inhibitor (MYCi) 10058-F4 or knockdown of MYC expression by short hairpin RNA (shRNA) both lead to a decrease in ITGA6 and ITGA6A levels in colorectal cancer cells, while overexpression of MYC enhances ITGA6 promoter activity. We also found that MYC inhibition decreases the epithelial splicing regulatory protein 2 (ESRP2) splicing factor at both the mRNA and protein levels. Chromatin immunoprecipitation revealed that the proximal promoter sequences of ITGA6 and ESRP2 were occupied by MYC and actively transcribed in colorectal cancer cells. Furthermore, expression studies in primary colorectal tumors and corresponding resection margins confirmed that the up-regulation of the ITGA6A subunit can be correlated with the increase in MYC and ESRP2. Taken together, our results demonstrate that the proto-oncogene MYC can regulate the promoter activation and splicing of the ITGA6 integrin gene through ESRP2 to favor the production of the pro-proliferative ITGA6A variant in colorectal cancer cells. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4c4acfcb9f3d3fd3456380840c63930Test http://www.mdpi.com/2072-6694/10/2/42Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b4c4acfcb9f3d3fd3456380840c63930 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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