A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells
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Kun Zhou1, Kevin W. Diebel1, Jon Holy1, Andrew Skildum1, Evan Odean1, Douglas A. Hicks2, Brent Schotl1, Juan E. Abrahante3, Monique A. Spillman4 and Lynne T. Bemis1
1Department of Biomedical Sciences, University of Minnesota, Duluth, MN, 55812, USA
2Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA
3University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN, 55455, USA
4Texas A&M University Medical School, Baylor University Medical Center, Dallas, TX, 75206 USA
Lynne T. Bemis, email: [email protected]
Keywords: tRNA fragments, BCAR3, ovarian cancer, tRF5-Glu, noncoding RNA
Received: January 10, 2017 Accepted: July 31, 2017 Published: September 08, 2017
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.
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