MiR-769-5p is associated with prostate cancer recurrence and modulates proliferation and apoptosis of cancer cells.

Abstract

MicroRNAs (miRs) are relevant in biological processes, including human prostate cancer. In the present study, the role of miR-769-5p and its targets in prostate cancer were explored. Publicly available data on expression of genes, miRs and disease-free survival of patients with prostate cancer were analyzed along with RNAseq of transfected cell lines. miR-769-5p expression was inversely associated with patient survival and in vitro assays indicated that its inhibition reduced the proliferation and increased apoptosis of prostate cancer cells. miR-769-5p was revealed to target Rho GTPase activating protein 10 (ARHGAP10) and increased expression of ARHGAP10 in tumors was determined to be associated with a favorable prognosis regarding disease-free survival. Of note, ARHGAP10 is a purported tumor suppressor in ovarian cancer, where it inhibits cell division cycle 42 (CDC42) activity and increases apoptosis. Similar effects were observed in prostate cancer cells, where miR-769-5p inhibition increased ARHGAP10 and led to reduced CDC42 activity. Furthermore, miR-769-5p inhibition increased apoptosis, which was partly reversed by additional knockdown of ARHGAP10. These results suggested that miR-769-5p is an oncogene targeting ARHGAP10, which in turn is a candidate tumor suppressor in prostate cancer.