RESUMEN
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.
Asunto(s)
MicroARNs/biosíntesis , Retinoblastoma/metabolismo , Línea Celular Tumoral , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Terapia Molecular Dirigida , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/patologíaRESUMEN
MicroRNAs (miRNAs) are short non-coding RNA transcripts that have the ability to regulate the expression of target genes, and have been shown to influence the development of various tumors. The purpose of our study is to identify aberrantly expressed miRNAs in retinoblastoma for the discovery of potential therapeutic targets for this disease, and to gain a greater understanding of the mechanisms driving retinoblastoma progression. We report 41 differentially expressed miRNAs (p<0.05) in 12 retinoblastomas as compared to three normal human retinae. Of these miRNAs, many are newly identified as being differentially expressed in retinoblastoma. Further, we report the validations of five of the most downregulated miRNAs in primary human retinoblastomas (p<0.05), human retinoblastoma cell lines, and mouse retinoblastoma cell lines. This serves as the largest and most comprehensive retinoblastoma miRNA analysis to date with corresponding clinical and pathological characteristics. This is an essential step in the discovery of miRNAs associated with retinoblastoma progression, and in the identification of potential therapeutic targets for this disease.