Upregulation of MiR-205 transcriptionally suppresses SMAD4 and PTEN and contributes to human ovarian cancer progression

被引:67
作者
Li, Juanni [1 ,2 ]
Hu, Kuan [3 ]
Gong, Guanghui [1 ,2 ]
Zhu, Ding [1 ,2 ]
Wang, Yixuan [1 ,2 ]
Liu, Hailing [1 ,2 ]
Wu, Xiaoying [1 ,2 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Pathol, Changsha, Hunan, Peoples R China
[2] Cent South Univ, Sch Basic Med Sci, Dept Pathol, Changsha, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Dept Hepatobiliary Surg, Changsha, Hunan, Peoples R China
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
中国国家自然科学基金;
关键词
MESENCHYMAL TRANSITION; METASTASIS; EXPRESSION; MICRORNAS; INHIBITION; APOPTOSIS; EMT;
D O I
10.1038/srep41330
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNAs (miRNAs) function as critical regulators of gene expression and their deregulation is associated with the development and progression of various cancers. This study aimed to investigate the biological role and mechanism of miR-205 in ovarian cancer (OC). MiR-205 was upregulated in OC tissues and cells in comparison to the controls. Meanwhile, overexpression of miR-205 was significantly associated with poor overall survival of OC patients. Functional study indicated that ectopic expression of miR-205 significantly promoted cell proliferation, migration, invasion and chemoresistance of OC cells. SMAD4 and PTEN were identified as direct targets of miR-205 using luciferase reporter assays, real-time PCR (qRT-PCR), and western blot. Most interestingly, in vivo studies indicated that miR-205 markedly promoted the growth and metastasis of tumors and the expression of miR-205 was also found to be inversely correlated with that of SMAD4 and PTEN in nude mice. Overall, we suggest that miR-205 functions as an oncogenic miRNA by directly binding to SMAD4 and PTEN, providing a novel target for the molecular treatment of ovarian cancer.
引用
收藏
页数:9
相关论文
共 41 条
  • [1] Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample
    Brain, Kate E.
    Smits, Stephanie
    Simon, Alice E.
    Forbes, Lindsay J.
    Roberts, Chris
    Robbe, Iain J.
    Steward, John
    White, Ceri
    Neal, Richard D.
    Hanson, Jane
    [J]. BMC CANCER, 2014, 14
  • [2] Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma
    Childs, Geoffrey
    Fazzari, Melissa
    Kung, Gloria
    Kawachi, Nicole
    Brandwein-Gensler, Margaret
    McLemore, Michael
    Chen, Quan
    Burk, Robert D.
    Smith, Richard V.
    Prystowsky, Michael B.
    Belbin, Thomas J.
    Schlecht, Nicolas F.
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2009, 174 (03) : 736 - 745
  • [3] Role of microRNA in epithelial to mesenchymal transition and metastasis and clinical perspectives
    Diaz-Lopez, Antonio
    Moreno-Bueno, Gema
    Cano, Amparo
    [J]. CANCER MANAGEMENT AND RESEARCH, 2014, 6 : 205 - 216
  • [4] miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes
    Dweep, Harsh
    Sticht, Carsten
    Pandey, Priyanka
    Gretz, Norbert
    [J]. JOURNAL OF BIOMEDICAL INFORMATICS, 2011, 44 (05) : 839 - 847
  • [5] Oncomirs - microRNAs with a role in cancer
    Esquela-Kerscher, A
    Slack, FJ
    [J]. NATURE REVIEWS CANCER, 2006, 6 (04) : 259 - 269
  • [6] MiR-378 Inhibits Progression of Human Gastric Cancer MGC-803 Cells by Targeting MAPK1 In Vitro
    Fei, Bojian
    Wu, Haorong
    [J]. ONCOLOGY RESEARCH, 2012, 20 (12) : 557 - 564
  • [7] microRNAs: Master Regulators as Potential Therapeutics in Cancer
    Garofalo, Michela
    Croce, Carlo M.
    [J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011, 2011, 51 : 25 - 43
  • [8] Targeting microRNAs in cancer: rationale, strategies and challenges
    Garzon, Ramiro
    Marcucci, Guido
    Croce, Carlo M.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (10) : 775 - 789
  • [9] Ovarian carcinoma pathology and genetics: recent advances
    Gilks, C. Blake
    Prat, Jaime
    [J]. HUMAN PATHOLOGY, 2009, 40 (09) : 1213 - 1223
  • [10] The role of miR-100 in regulating apoptosis of breast cancer cells
    Gong, Yi
    He, Tianliang
    Yang, Lu
    Yang, Geng
    Chen, Yulei
    Zhang, Xiaobo
    [J]. SCIENTIFIC REPORTS, 2015, 5