Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells
Retinoblastoma (RB) is a primary childhood eye cancer. HMGA2 shows promise as a molecule for targeted therapy. The involvement of miRNAs in genome-level molecular dys-regulation in HMGA2 -silenced RB cells is poorly understood. Through miRNA expression microarray profiling, and an integrated array a...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2014-01-01
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| Series: | Bioinformatics and Biology Insights |
| Online Access: | https://doi.org/10.4137/BBI.S16958 |
| _version_ | 1818240185395052544 |
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| author | Nalini Venkatesan P. R. Deepa Madavan Vasudevan Vikas Khetan Ashwin M. Reddy Subramanian Krishnakumar |
| author_facet | Nalini Venkatesan P. R. Deepa Madavan Vasudevan Vikas Khetan Ashwin M. Reddy Subramanian Krishnakumar |
| author_sort | Nalini Venkatesan |
| collection | DOAJ |
| description | Retinoblastoma (RB) is a primary childhood eye cancer. HMGA2 shows promise as a molecule for targeted therapy. The involvement of miRNAs in genome-level molecular dys-regulation in HMGA2 -silenced RB cells is poorly understood. Through miRNA expression microarray profiling, and an integrated array analysis of the HMGA2 -silenced RB cells, the dysregulated miRNAs and the miRNA-target relationships were modelled. Loop network analysis revealed a regulatory association between the transcription factor ( SOX5 ) and the deregulated miRNAs imiR-29a, miR-9*, miR-9-3 ). Silencing of HMGA2 deregulated the vital oncomirs ( miR-7, miR-331, miR-26a, miR-221, miR-17∼92 and miR-106b∼25 ) in RB cells. From this list, the role of the miR-106b∼25 cluster was examined further for its expression in primary RB tumor tissues (n = 20). The regulatory targets of miR-106b∼25 cluster namely p21 (cyclin-dependent kinase inhibitor) and BIM (pro-apoptotic gene) were elevated, and apoptotic cell death was observed, in RB tumor cells treated with the specific antagomirs of the miR-106b∼25 cluster. Thus, suppression of miR-106b∼25 cluster controls RB tumor growth. Taken together, HMGA2 mediated anti-tumor effect present in RB is, in part, mediated through the miR-106b∼25 cluster. |
| first_indexed | 2024-12-12T13:09:25Z |
| format | Article |
| id | doaj.art-379cf519df7543a7881c76893c62e35e |
| institution | Directory Open Access Journal |
| issn | 1177-9322 |
| language | English |
| last_indexed | 2024-12-12T13:09:25Z |
| publishDate | 2014-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Bioinformatics and Biology Insights |
| spelling | doaj.art-379cf519df7543a7881c76893c62e35e2022-12-22T00:23:33ZengSAGE PublishingBioinformatics and Biology Insights1177-93222014-01-01810.4137/BBI.S16958Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma CellsNalini Venkatesan0P. R. Deepa1Madavan Vasudevan2Vikas Khetan3Ashwin M. Reddy4Subramanian Krishnakumar5Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India.Department of Biological Sciences, Birla Institute of Technology and Science (BITS) – Pilani, Rajasthan, India.Bionivid Technology [P] Ltd, Kasturi Nagar, Bangalore, India.Sri Bhagawan Mahavir Department of Vitreoretinal and Ocular Oncology, Medical Research Foundation, Sankara Nethralaya, Chennai, India.Department of Ophthalmology, Barts Health NHS Trust, London, UK.Larsen and Toubro Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.Retinoblastoma (RB) is a primary childhood eye cancer. HMGA2 shows promise as a molecule for targeted therapy. The involvement of miRNAs in genome-level molecular dys-regulation in HMGA2 -silenced RB cells is poorly understood. Through miRNA expression microarray profiling, and an integrated array analysis of the HMGA2 -silenced RB cells, the dysregulated miRNAs and the miRNA-target relationships were modelled. Loop network analysis revealed a regulatory association between the transcription factor ( SOX5 ) and the deregulated miRNAs imiR-29a, miR-9*, miR-9-3 ). Silencing of HMGA2 deregulated the vital oncomirs ( miR-7, miR-331, miR-26a, miR-221, miR-17∼92 and miR-106b∼25 ) in RB cells. From this list, the role of the miR-106b∼25 cluster was examined further for its expression in primary RB tumor tissues (n = 20). The regulatory targets of miR-106b∼25 cluster namely p21 (cyclin-dependent kinase inhibitor) and BIM (pro-apoptotic gene) were elevated, and apoptotic cell death was observed, in RB tumor cells treated with the specific antagomirs of the miR-106b∼25 cluster. Thus, suppression of miR-106b∼25 cluster controls RB tumor growth. Taken together, HMGA2 mediated anti-tumor effect present in RB is, in part, mediated through the miR-106b∼25 cluster.https://doi.org/10.4137/BBI.S16958 |
| spellingShingle | Nalini Venkatesan P. R. Deepa Madavan Vasudevan Vikas Khetan Ashwin M. Reddy Subramanian Krishnakumar Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells Bioinformatics and Biology Insights |
| title | Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells |
| title_full | Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells |
| title_fullStr | Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells |
| title_full_unstemmed | Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells |
| title_short | Integrated Analysis of Dysregulated miRNA-Gene Expression in -Silenced Retinoblastoma Cells |
| title_sort | integrated analysis of dysregulated mirna gene expression in silenced retinoblastoma cells |
| url | https://doi.org/10.4137/BBI.S16958 |
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