MicroRNA-532 and microRNA-3064 inhibit cell proliferation and invasion by acting as direct regulators of human telomerase reverse transcriptase in ovarian cancer

• Published in: PloS one Vol. 12; no. 3; p. e0173912
• Main Authors: Bai, Lin, Wang, Hui, Wang, Ai-Hua, Zhang, Luo-Ying, Bai, Jie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.03.2017; Public Library of Science (PLoS)
• Subjects: 3' Untranslated regions; Analysis; Animals; Binding sites; Bioinformatics; Biology and life sciences; Cancer; Care and treatment; Cell proliferation; Cell Proliferation - genetics; Cell survival; Complementary DNA; Correlation analysis; Development and progression; Epigenetics; Female; Gastric cancer; Gene expression; Genetic aspects; Genetic regulation; Gynecology; Heterografts; Humans; Infrared imaging systems; Metastasis; Mice; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - physiology; miRNA; Neoplasm Invasiveness; Obstetrics; Oligonucleotides; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Physiological aspects; Regulators; Research and Analysis Methods; Reverse transcriptase; Ribonucleic acid; RNA; RNA-directed DNA polymerase; siRNA; Stomach cancer; Survival Analysis; Telomerase; Telomerase reverse transcriptase; Tissues; Tumors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0173912

Human telomerase reverse transcriptase (hTERT) plays a crucial role in ovarian cancer (OC) progression. However, the mechanisms underlying hTERT upregulation in OC, and the specific microRNAs (miRNAs) involved in the regulation of hTERT in OC cells, remains unclear. We performed a bioinformatics search to identify potential miRNAs that bind to the 3'-untranslated region (3'-UTR) region of the hTERT mRNA. We examined the expression levels of miR-532/miR-3064 in OC tissues and normal ovarian tissues, and analyzed the correlation between miRNA expression and OC patient outcomes. The impacts of miR-532/miR-3064 on hTERT expression were evaluated by western blot analysis and hTERT 3'-UTR reporter assays. We investigated the effects of miR-532/miR-3064 on proliferation and invasion in OC cells. We found that miR-532 and miR-3064 are down-regulated in OC specimens. We observed a significant association between reduced miR-532/miR-3064 expression and poorer survival of patients with OC. We confirmed that in OC cells, these two miRNAs downregulate hTERT levels by directly targeting its 3'-UTR region, and inhibited proliferation, EMT and invasion of OC cells. In addition, the overexpression of the hTERT cDNA lacking the 3'-UTR partially restored miR-532/miR-3064-inhibited OC cell proliferation and invasion. The silencing of hTERT by siRNA oligonucleotides abolished these malignant features, and phenocopied the effects of miR-532/miR-3064 overexpression. Furthermore, overexpression of miR-532/miR-3064 inhibits the growth of OC cells in vivo. Our findings demonstrate a miR-532/miR-3064-mediated mechanism responsible for hTERT upregulation in OC cells, and reveal a possibility of targeting miR-532/miR-3064 for future treatment of OC.