Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression

It has been demonstrated that microRNA (miR)-133a is downregulated in a number of human malignancies and is closely associated with the progression of tumors. The present study was conducted to investigate the contribution of miR-133a to the initiation and malignant progression of human epithelial ovarian cancer (EOC). Quantitative polymerase chain reaction was employed to detect the expression of miR-133a in the human EOC OVCAR-3 cell line, normal human ovarian surface epithelial (tsT) cells and 96 tissue samples, including 70 EOC tissues and 26 normal ovarian tissue sections. Additionally, analysis of the correlation between miR-133a levels and clinicopathological characteristics was carried out. The effect of miR-133a on cell viability, apoptosis, invasion and migration was investigated following transfection with miR-133a mimics and negative control small interfering RNA in OVCAR-3 cells. Marked downregulation of miR-133a was observed in the OVCAR-3 cell line and primary tumor samples, and it was found that reduced miR-133a expression significantly correlated with advanced clinical stages, poor histological differentiation and lymph node metastasis. Furthermore, OVCAR-3 cell viability, invasion and migration were significantly inhibited, while cell apoptosis was increased, following transfection of miR-133a mimics. The present study reveals the critical role that miR-133a plays in EOC pathogenesis and development, indicating that it may act as a promising biomarker for predicting EOC progression and as a potential target for gene therapy.

[1]  K. Chao,et al.  MicroRNA‐138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF‐1α , 2013, International journal of cancer.

[2]  Anthony E Brenneman,et al.  Screening for ovarian cancer. , 2013, JAAPA : official journal of the American Academy of Physician Assistants.

[3]  D. Marsh,et al.  Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer , 2012, BMC Cancer.

[4]  N. Seki,et al.  Functional role of LASP1 in cell viability and its regulation by microRNAs in bladder cancer. , 2012, Urologic oncology.

[5]  Nahum Sonenberg,et al.  The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC , 2012, Nature Structural &Molecular Biology.

[6]  N. Seki,et al.  The functional significance of miR-1 and miR-133a in renal cell carcinoma. , 2012, European journal of cancer.

[7]  T. Zhu,et al.  Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion , 2012, BMC Cancer.

[8]  N. Seki,et al.  Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma , 2011, Journal of Human Genetics.

[9]  N. Seki,et al.  Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer , 2011, British Journal of Cancer.

[10]  Y. Okamoto,et al.  Identification of novel molecular targets regulated by tumor suppressive miR-1/miR-133a in maxillary sinus squamous cell carcinoma. , 2011, International journal of oncology.

[11]  Zhumei Cui,et al.  miR-21 down-regulation promotes apoptosis and inhibits invasion and migration abilities of OVCAR3 cells. , 2011, Clinical and investigative medicine. Medecine clinique et experimentale.

[12]  N. Seki,et al.  The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer , 2011, British Journal of Cancer.

[13]  Masayuki Kano,et al.  miR‐145, miR‐133a and miR‐133b: Tumor‐suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma , 2010, International journal of cancer.

[14]  Yu Huang,et al.  MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. , 2010, International journal of molecular medicine.

[15]  Y. Okamoto,et al.  Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. , 2010, International journal of oncology.

[16]  H. Lodish,et al.  Distinct roles for miR‐1 and miR‐133a in the proliferation and differentiation of rhabdomyosarcoma cells , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  N. Seki,et al.  miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer , 2010, British Journal of Cancer.

[18]  Ann L Oberg,et al.  Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states , 2009, BMC Cancer.

[19]  M. Iorio,et al.  MicroRNAs and future therapeutic applications in cancer. , 2009, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[20]  M. Loda,et al.  miR-29b Expression Is Associated With Disease-Free Survival in Patients With Ovarian Serous Carcinoma , 2009, International Journal of Gynecologic Cancer.

[21]  T. Wong,et al.  Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling , 2008, International journal of cancer.

[22]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[23]  S. Pecorelli,et al.  History of the FIGO cancer staging system , 2008, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[24]  M. Jovanović,et al.  miRNAs and apoptosis: RNAs to die for , 2006, Oncogene.

[25]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  V. Ambros.  MicroRNA Pathways in Flies and Worms Growth, Death, Fat, Stress, and Timing , 2003, Cell.

[27]  D A Scudiero,et al.  Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. , 1988, Cancer research.

[28]  H. Jeejeebhoy.  Immunological studies of women with primary breast carcinoma , 1975, International journal of cancer.

[29]  H. Cui,et al.  MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. , 2011, Asian Pacific journal of cancer prevention : APJCP.

[30]  Hong-zhao Li,et al.  Differential miRNA expression profiles in bladder urothelial carcinomas. , 2010, Asian Pacific journal of cancer prevention : APJCP.

[31]  D. Clarke‐Pearson.  Clinical practice. Screening for ovarian cancer. , 2009, The New England journal of medicine.

[32]  A. Karseladze.  [WHO histological classification of ovarian tumors. Geneva, 1999 (R.E.Scully, L.H.Sobin]. , 2005, Arkhiv patologii.

[33]  W. Hoskins.  Prospective on ovarian cancer: Why prevent? , 1995, Journal of cellular biochemistry. Supplement.