title: MiR-34a suppresses ovarian cancer proliferation and motility by targeting AXL.
abstract: Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-34 family is directly transactivated by tumor suppressor p53 which is frequently mutated in various cancers; however, the effect of miR-34a on the ovarian cancer cells remains unclear. The aim of the paper was to study the expression of miR-34a in ovarian cancer and miR-34a's relation to the cell proliferation and metastasis in ovarian cancer in vitro. miR-34a expression was determined by quantitative RT-PCR in a panel of 60 human ovarian cancer samples. Functional characterization of miR-34a was accomplished by reconstitution of miR-34a expression in ovarian cancer cells by determining changes in proliferation, migration, and invasion. Our results showed that miR-34a is downregulated in ovarian cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of miR-34a was significantly lower in ovarian cancer cell lines in comparison with normal human fallopian tube epithelial cell line. The 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay revealed significant cell proliferation inhibition in miR-34a transfectant compared with the control from HO8910 and SKOV3 cells, which displayed lowest expressions of miR-34a. Furthermore, the transwell assay also showed significant cell migration inhibition in miR-34a transfectant, compared with cell lines transfected with NC. Overexpression of miR-34a led to the inhibition of AXL expression, indicating that AXL is a target gene for miR-34a. Our data suggest that miR-34a may function as a tumor suppressor through repression of oncogenic AXL in ovarian cancer.
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China. drshixj6@163.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Ling
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL; MiR-34a; Migration; Ovarian cancer; P53; Proliferation