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.