MiR-34a suppresses ovarian cancer proliferation and motility by targeting AXL
详细信息    查看全文
  • 作者:Rui Li ; Xuejun Shi ; Fengyu Ling ; Chunguang Wang ; Junxia Liu ; Wei Wang
  • 关键词:Ovarian cancer ; MiR ; 34a ; AXL ; P53 ; Proliferation ; Migration
  • 刊名:Tumor Biology
  • 出版年:2015
  • 出版时间:September 2015
  • 年:2015
  • 卷:36
  • 期:9
  • 页码:7277-7283
  • 全文大小:938 KB
  • 参考文献:1.Brouwer-Visser J, Lee J, McCullagh K, Cossio MJ, Wang Y, Huang GS. Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer. PLoS One. 2014;9(6):e100165.PubMed PubMedCentral CrossRef
    2.Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, et al. MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008;14:2690–5.PubMed CrossRef
    3.Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61:183–203.PubMed PubMedCentral CrossRef
    4.Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13:271–82.PubMed
    5.Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113:673–6.PubMed CrossRef
    6.Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMed CrossRef
    7.Wang X, Li J, Dong K, Lin F, Long M, Ouyang Y, et al. Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal. 2015;27(3):443–52.PubMed CrossRef
    8.Chen WY, Liu SY, Chang YS, Yin JJ, Yeh HL, Mouhieddine TH, et al. MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer. Oncotarget. 2015;6(1):441–57.PubMed PubMedCentral CrossRef
    9.Xiao X, Chen B, Liu X, Liu P, Zheng G, Ye F, et al. Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a. PLoS One. 2014;9(11), e112720.PubMed PubMedCentral CrossRef
    10.Li X, Zhao H, Zhou X, Song L. Inhibition of lactate dehydrogenase A by microRNA-34a resensitizes colon cancer cells to 5-fluorouracil. Mol Med Rep. 2015;11(1):577–82.PubMed
    11.Wu MY, Fu J, Xiao X, Wu J, Wu RC. MiR-34a regulates therapy resistance by targeting HDAC1 and HDAC7 in breast cancer. Cancer Lett. 2014;354(2):311–9.PubMed CrossRef
    12.Suh YA, Jo SY, Lee HY, Lee C. Inhibition of IL-6/STAT3 axis and targeting Axl and Tyro3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells. Int J Oncol. 2015;46(3):1405–11.PubMed
    13.Concepcion CP, Han Y-C, Mu P, Bonetti C, Yao E, D’andrea A, et al. Intact p53-dependent responses in miR-34-deficient mice. PLoS Genet. 2012;8, e1002797.PubMed PubMedCentral CrossRef
    14.Liu N, Landreh M, Cao K, Abe M, Hendriks G-J, Kennerdell JR, et al. The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature. 2012;482:519–23.PubMed PubMedCentral CrossRef
    15.Tarasov V, Jung P, Verdoodt B, et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 2007;6:1586–93.PubMed CrossRef
    16.Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17:1298–307.PubMed CrossRef
    17.Raver-Shapira N, Marciano E, Meiri E, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26:731–43.PubMed CrossRef
    18.Cheung HH, Lee TL, Davis AJ, Taft DH, Rennert OM, Chan WY. Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer. 2010;102:419–27.PubMed PubMedCentral CrossRef
    19.Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68:4123–32.PubMed CrossRef
    20.Mudduluru G, Ceppi P, Kumarswamy R, Scagliotti GV, Papotti M, Allgayer H. Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer. Oncogene. 2011;30:2888–99.PubMed CrossRef
    21.Hafizi S, Dahlback B. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. FEBS J. 2006;273:5231–44.PubMed CrossRef
  • 作者单位:Rui Li (1)
    Xuejun Shi (1)
    Fengyu Ling (1)
    Chunguang Wang (1)
    Junxia Liu (1)
    Wei Wang (1)
    Ming Li (1)

    1. Department of Oncology, Yongchuan Hospital Affiliated to Chongqing Medical University, No. 439, Xuanhua Road, Chongqing, 402160, China
  • 刊物主题:Cancer Research;
  • 出版者:Springer Netherlands
  • ISSN:1423-0380
文摘
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.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700