Lee Daniel
Medical Oncology Service and The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Exp Ther Med. 2021 Apr;21(4):335. doi: 10.3892/etm.2021.9766. Epub 2021 Feb 8.
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 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.
微小RNA(miR)与包括人类前列腺癌在内的生物过程相关。在本研究中,探讨了miR-769-5p及其靶点在前列腺癌中的作用。分析了前列腺癌患者基因、miR表达及无病生存的公开可用数据,并对转染细胞系进行了RNA测序。miR-769-5p的表达与患者生存呈负相关,实验表明其抑制作用可降低前列腺癌细胞的增殖并增加其凋亡。研究发现miR-769-5p靶向Rho GTP酶激活蛋白10(ARHGAP10),肿瘤中ARHGAP10表达增加被确定与无病生存的良好预后相关。值得注意的是,ARHGAP10在卵巢癌中被认为是一种肿瘤抑制因子,它可抑制细胞分裂周期42(CDC42)的活性并增加凋亡。在前列腺癌细胞中也观察到了类似的效应,miR-769-5p抑制可增加ARHGAP10并导致CDC42活性降低。此外,miR-769-5p抑制可增加凋亡,而ARHGAP10的进一步敲低可部分逆转这种凋亡。这些结果表明,miR-769-5p是一种靶向ARHGAP10的癌基因,而ARHGAP10反过来又是前列腺癌中的候选肿瘤抑制因子。