التفاصيل البيبلوغرافية
العنوان: |
Data from miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells |
المؤلفون: |
Wafik S. El-Deiry, David T. Dicker, Margret B. Einarson, Avital Lev, Yan Zhou, Michael J. Slifker, Amriti R. Lulla |
بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
سنة النشر: |
2023 |
الوصف: |
CDK4/6 targeting is a promising therapeutic strategy under development for various tumor types. In this study, we used computational methods and The Cancer Genome Atlas dataset analysis to identify novel miRNAs that target CDK4/6 and exhibit potential for therapeutic development in colorectal cancer. The 3′UTR of CDK4/6 mRNAs are targeted by a family of miRNAs, which includes miR-6883-5p, miR-149*, miR-6785-5p, and miR-4728-5p. Ectopic expression of miR-6883-5p or miR-149* downregulated CDK4 and CDK6 levels in human colorectal cancer cells. RNA-seq analysis revealed an inverse relationship between the expression of CDK4/6 and miR-149* and intronic miRNA-6883-5p encoding the clock gene PER1 in colorectal cancer patient samples. Restoring expression of miR-6883-5p and miR-149* blocked cell growth leading to G0–G1 phase cell-cycle arrest and apoptosis in colorectal cancer cells. CDK4/6 targeting by miR-6883-5p and miR-149* could only partially explain the observed antiproliferative effects. Notably, both miRNAs synergized with the frontline colorectal cancer chemotherapy drug irinotecan. Further, they resensitized mutant p53-expressing cell lines resistant to 5-fluorouracil. Taken together, our results established the foundations of a candidate miRNA-based theranostic strategy to improve colorectal cancer management. Cancer Res; 77(24); 6902–13. ©2017 AACR. |
URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_________::245263566ba9a208e4fe138457b86c5e https://doi.org/10.1158/0008-5472.c.6509301.v1 |
حقوق: |
OPEN |
رقم الأكسشن: |
edsair.doi...........245263566ba9a208e4fe138457b86c5e |
قاعدة البيانات: |
OpenAIRE |