MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma.

Retinoblastoma is the most common pediatric cancer of the eye. Currently, the chemotherapeutic treatments for retinoblastoma are broad-based drugs such as vincristine, carboplatin, or etoposide. However, therapies targeted directly to aberrant signaling pathways may provide more effective therapy for this disease. The purpose of our study is to illustrate the relationship between the expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis. We are the first to confirm an inhibitory effect of miR-449a and -449b in retinoblastoma by demonstrating significantly impaired proliferation and increased apoptosis of tumor cells when these miRNAs are overexpressed. This study suggests that these miRNAs could serve as viable therapeutic targets for retinoblastoma treatment.

[1]  Chenguang Wang,et al.  Minireview: Cyclin D1: normal and abnormal functions. , 2004, Endocrinology.

[2]  Anders Krogh,et al.  miR-449 inhibits cell proliferation and is down-regulated in gastric cancer , 2011, Molecular Cancer.

[3]  T. Kivelä The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death , 2009, British Journal of Ophthalmology.

[4]  Zengrong Liu,et al.  Dynamical Behaviors of Rb-E2F Pathway Including Negative Feedback Loops Involving miR449 , 2012, PloS one.

[5]  Xiaodong Gu,et al.  miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. , 2013, Oncology reports.

[6]  M. Dobbelstein,et al.  E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis , 2010, Cell Death and Differentiation.

[7]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Yan Wang,et al.  Correlation of overexpression of HMGA1 and HMGA2 with poor tumor differentiation, invasion, and proliferation associated with let-7 down-regulation in retinoblastomas. , 2010, Human pathology.

[9]  H. Hermeking The miR-34 family in cancer and apoptosis , 2010, Cell Death and Differentiation.

[10]  J. Mendell miRiad Roles for the miR-17-92 Cluster in Development and Disease , 2008, Cell.

[11]  Qiang Yu,et al.  miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. , 2009, Genes & development.

[12]  D. Ellison,et al.  Changes in Retinoblastoma Cell Adhesion Associated with Optic Nerve Invasion , 2009, Molecular and Cellular Biology.

[13]  J. M. Thomson,et al.  miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma. , 2011, Genes & development.

[14]  C. Shields,et al.  Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy , 2010, Current opinion in ophthalmology.

[15]  P. Boutros,et al.  Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues , 2009, Laboratory Investigation.

[16]  M. Soares,et al.  Differentially expressed miRNAs in retinoblastoma. , 2013, Gene.

[17]  P. Chévez-Barrios,et al.  Metastatic and nonmetastatic models of retinoblastoma. , 2000, The American journal of pathology.

[18]  J. O'Brien,et al.  Differential microRNA-34a expression and tumor suppressor function in retinoblastoma cells. , 2009, Investigative ophthalmology & visual science.