Oncotarget

Research Papers:

A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells

Kun Zhou, Kevin W. Diebel, Jon Holy, Andrew Skildum, Evan Odean, Douglas A. Hicks, Brent Schotl, Juan E. Abrahante, Monique A. Spillman and Lynne T. Bemis _

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Oncotarget. 2017; 8:95377-95391. https://doi.org/10.18632/oncotarget.20709

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Abstract

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

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.


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