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MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines
BACKGROUND: Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205057/ https://www.ncbi.nlm.nih.gov/pubmed/21939554 http://dx.doi.org/10.1186/1757-2215-4-17 |
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author | Kumar, Smriti Kumar, Arooshi Shah, Parag P Rai, Shesh N Panguluri, Siva K Kakar, Sham S |
author_facet | Kumar, Smriti Kumar, Arooshi Shah, Parag P Rai, Shesh N Panguluri, Siva K Kakar, Sham S |
author_sort | Kumar, Smriti |
collection | PubMed |
description | BACKGROUND: Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. METHODS: The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs) between cis-platin sensitive (A2780), and cis-platin resistant (A2780/CP70) cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. RESULTS: Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. CONCLUSIONS: Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated proteasomal pathway, Wnt signaling, mTOR signaling, Notch signaling, apoptosis, and many other signaling pathways. Manipulation of one or more of these miRNAs could be an important approach for ovarian cancer chemotherapy. |
format | Online Article Text |
id | pubmed-3205057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32050572011-11-01 MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines Kumar, Smriti Kumar, Arooshi Shah, Parag P Rai, Shesh N Panguluri, Siva K Kakar, Sham S J Ovarian Res Research BACKGROUND: Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. METHODS: The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs) between cis-platin sensitive (A2780), and cis-platin resistant (A2780/CP70) cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. RESULTS: Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. CONCLUSIONS: Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated proteasomal pathway, Wnt signaling, mTOR signaling, Notch signaling, apoptosis, and many other signaling pathways. Manipulation of one or more of these miRNAs could be an important approach for ovarian cancer chemotherapy. BioMed Central 2011-09-22 /pmc/articles/PMC3205057/ /pubmed/21939554 http://dx.doi.org/10.1186/1757-2215-4-17 Text en Copyright ©2011 Kumar et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Kumar, Smriti Kumar, Arooshi Shah, Parag P Rai, Shesh N Panguluri, Siva K Kakar, Sham S MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title | MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title_full | MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title_fullStr | MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title_full_unstemmed | MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title_short | MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
title_sort | microrna signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205057/ https://www.ncbi.nlm.nih.gov/pubmed/21939554 http://dx.doi.org/10.1186/1757-2215-4-17 |
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