MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

• Published in: Drug design, development and therapy development and therapy, 2016-01, Vol.10 (Issue 1), p.71-79
• Main Authors: Qin, Xian, Wan, Yajun, Wang, Saiying, Xue, Min
• Format: Article
• Language: English
• Subjects: ABL2; Animals; Apoptosis; Biotechnology; Breast cancer; cancer migration; cancer proliferation; Cell division; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cervical cancer; Cervical carcinoma; Cervix; Chromosome 5; Developing countries; Down-Regulation; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gynecology; HeLa Cells; Human papillomavirus; Humans; LDCs; Lentivirus - genetics; Liver cancer; Lung cancer; Medical prognosis; Mice; Mice, Nude; MicroRNAs; MicroRNAs - genetics; miR-125a-5p; miRNA; Obstetrics; Original Research; Pancreatic cancer; Polymerase chain reaction; Prostate cancer; Protein-Tyrosine Kinases - genetics; Real time; Real-Time Polymerase Chain Reaction; Regulatory mechanisms (biology); Reverse Transcriptase Polymerase Chain Reaction; Reverse transcription; Ribonucleic acid; RNA; RNA, Small Interfering - administration & dosage; siRNA; Ski protein; Transplantation; Tumor cell lines; Up-Regulation; Uterine Cervical Neoplasms - genetics; Western blotting; Womens health
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S93104

In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p) in human cervical carcinoma. The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2), in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration. miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration. The molecular pathway of miR-125a-5p/ABL2 plays an important role in human cervical carcinoma. Targeting miR-125a-5p/ABL2 pathway may provide a new treatment strategy for patients with cervical carcinoma.