A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells
| Autor: | Douglas A. Hicks, Kevin W. Diebel, Lynne T. Bemis, Evan Odean, Juan E. Abrahante, Kun Zhou, Jon M Holy, Brent Schotl, Monique A. Spillman, Andrew J Skildum |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Messenger RNA Cell growth Biology medicine.disease Non-coding RNA noncoding RNA 03 medical and health sciences 030104 developmental biology Breast cancer ovarian cancer Oncology tRF5-Glu microRNA Cancer cell BCAR3 Cancer research medicine Ovarian cancer Research Paper tRNA fragments |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Kun Zhou 1 , Kevin W. Diebel 1 , Jon Holy 1 , Andrew Skildum 1 , Evan Odean 1 , Douglas A. Hicks 2 , Brent Schotl 1 , Juan E. Abrahante 3 , Monique A. Spillman 4 and Lynne T. Bemis 1 1 Department of Biomedical Sciences, University of Minnesota, Duluth, MN, 55812, USA 2 Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA 3 University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, 55455, USA 4 Texas A&M University Medical School, Baylor University Medical Center, Dallas, TX, 75206 USA Correspondence to: Lynne T. Bemis, email: ltbemis@d.umn.edu Keywords: tRNA fragments, BCAR3, ovarian cancer, tRF5-Glu, noncoding RNA Received: January 10, 2017 Accepted: July 31, 2017 Published: September 08, 2017 ABSTRACT Ovarian cancer is a complex disease marked by tumor heterogeneity, which contributes to difficulties in diagnosis and treatment. New molecular targets and better molecular profiles defining subsets of patients are needed. tRNA fragments (tRFs) offer a recently identified group of noncoding RNAs that are often as abundant as microRNAs in cancer cells. Initially their presence in deep sequencing data sets was attributed to the breakdown of mature tRNAs, however, it is now clear that they are actively generated and function in multiple regulatory events. One such tRF, a 5’ fragment of tRNA-Glu-CTC (tRF5-Glu), is processed from the mature tRNA-Glu and is shown in this study to be expressed in ovarian cancer cells. We confirmed that tRF5-Glu binds directly to a site in the 3’UTR of the Breast Cancer Anti-Estrogen Resistance 3 (BCAR3) mRNA thereby down regulating its expression. BCAR3 has not previously been studied in ovarian cancer cells and our studies demonstrate that inhibiting BCAR3 expression suppresses ovarian cancer cell proliferation. Furthermore, mimics of tRF5-Glu were found to inhibit proliferation of ovarian cancer cells. In summary, BCAR3 and tRF5-Glu contribute to the complex tumor heterogeneity of ovarian cancer cells and may provide new targets for therapeutic intervention. |
| Databáze: | OpenAIRE |
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