MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2
نویسندگان
چکیده
BACKGROUND In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p) in human cervical carcinoma. METHODS 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. RESULTS 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. CONCLUSION 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.
منابع مشابه
Downregulation of TMEM40 by miR-138-5p suppresses cell proliferation and mobility in clear cell renal cell carcinoma
Background: Clear cell renal cell carcinoma (ccRCC) represents approximately 70% of RCC,as the most frequent histological subtype of RCC. MiR-138-5p, a tumor-related microRNA (miRNA), has been reported to be implicated in the diverse types of human malignancies, but its role in ccRCCremains unclear. Objective: The study was designed to investigate the function...
متن کاملLowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up-regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c-Raf
Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical c...
متن کاملIdentification of miR‑125a‑5p as a tumor suppressor of renal cell carcinoma, regulating cellular proliferation, migration and apoptosis.
miR‑125a‑5p has been previously described as a tumor suppressor in numerous malignancies, however the expression and function of miR‑125a‑5p in renal cell carcinoma (RCC) remains to be elucidated. In the present study, to explore the potential role of miR‑125a‑5p in RCC, quantitative polymerase chain reaction was used to determine the expression levels of miR‑125a‑5p in renal cancer tissues. Th...
متن کاملMicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab.
PURPOSE MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu...
متن کاملMicroRNA-199a-5p inhibits VEGF-induced tumorigenesis through targeting oxidored-nitro domain-containing protein 1 in human HepG2 cells.
VEGF induces deterioration of hepatocellular carcinoma (HCC) by enhancing cell proliferation and migration. MicroRNAs regulate many cellular processes. In this study, we examined the regulation of tumorigenesis in HCC cells by microRNAs in relation to the effect of VEGF. Differences in microRNA expression between HepG2 and THLE-3 cells were characterized by microarray analysis. The results show...
متن کامل