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Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation.

ABSTRACT: Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of post-transcriptional events that occur after the initiating genetic lesions could further define the rapidly aggressive growth displayed by retinoblastoma tumors. In this study, we used two phenotypically different retinoblastoma cell lines to elucidate the roles of miRNA-31 and miRNA-200a in tumor proliferation. Our approach confirmed that miRNAs-31 and -200a expression is significantly reduced in human retinoblastomas. Moreover, overexpression of these two miRNAs restricts the expansion of a highly proliferative cell line (Y79), but does not restrict the growth rate of a less aggressive cell line (Weri1). Gene expression profiling of miRNA-31 and/or miRNA-200a-overexpressing cells identified differentially expressed mRNAs associated with the divergent response of the two cell lines. This work has the potential to enhance the development of targeted therapeutic approaches for retinoblastoma and improve the efficacy of treatment.

SUBMITTER: Montoya V

PROVIDER: S-EPMC4574557 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation.

Montoya Vanessa V Fan Hanli H Bryar Paul J PJ Weinstein Joanna L JL Mets Marilyn B MB Feng Gang G Martin Joshua J Martin Alissa A Jiang Hongmei H Laurie Nikia A NA

PloS one 20150917 9

Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of p ...[more]

PMID: 26379276

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Project description:Objective:This study was set out to explore the expression and related mechanism of XIST and miR-200a-3p in retinoblastoma (Rb). Patients and Methods:Fifty-four children with Rb who came to our hospital for surgery from January 2018 to September 2019 were collected. In addition, Rb cells and human retinal epithelial cells were purchased. XIST-siRNA (si-XIST), XIST-shRNA (sh-XIST), empty vector plasmid (siRNA-NC), miR-200a-3p-mimics and miR -200a-3p-inhibition were transfected into Y79 cells. The expression of XIST and miR-200a-3p in the samples were determined by qRT-PCR. ?-catenin, cyclin B1, cyclin D1, Bax, Caspase-3, N-cadherin, vimentin, Snail, E-Cadherin and ZO-1 protein levels were measured by WB. MTT, Transwell and flow cytometry were utilized to detect cell proliferation, invasion, and apoptosis, respectively. Results:XIST was highly expressed while miR-200a-3p was lowly expressed in patients' tissues, and the AUC of both was over 0.8. XIST and miR-200a-3p was related to differentiation degree in Rb patients. Y79 cells were selected for transfection. Compared with the siRNA-NC group, XIST was significantly reduced in the siRNA-XIST group, and it was significantly increased in the shRNA-XIST group (P<0.01). The proliferation capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated. The apoptosis rate of siRNA-XIST group was significantly up-regulated, while that of shRNA-XIST group was decreased (P<0.001). The invasive capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated (P<0.001). Silencing XIST and over-expressed miR-200a-3p could inhibit cell epithelial-mesenchymal transition (EMT), proliferation, invasion, and promote apoptosis. WB detection showed that Carboplatin + LncRNA XIST intervention group could more significantly inhibit ?-catenin, cyclin B1, cyclin D1, N-cadherin, vimentin, Snail protein, and promote the up-regulation of Bax, Caspase-3, E-Cadherin and ZO-1 expression. Conclusion:Inhibition of XIST expression can up-regulate miR-200a-3p-mediated PI3K-Akt/MAPK-ERK signaling pathway and affect cell EMT, proliferation, invasion, and apoptosis, which is expected to be a potential therapeutic target for Rb.

Dataset Information

Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation.

Publications

Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation.

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