MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: Kumar Smriti, Kumar Arooshi, Shah Parag P, Rai Shesh N, Panguluri Siva K, Kakar Sham S
Format: Article
Language:English
Published: BMC 2011-09-01
Series:Journal of Ovarian Research
Online Access:http://www.ovarianresearch.com/content/4/1/17
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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 DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>
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spelling doaj.art-ba98d63e46084d2a85457ef5fa0c7fca2023-01-02T22:29:15ZengBMCJournal of Ovarian Research1757-22152011-09-01411710.1186/1757-2215-4-17MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell linesKumar SmritiKumar ArooshiShah Parag PRai Shesh NPanguluri Siva KKakar Sham S<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.ovarianresearch.com/content/4/1/17
spellingShingle 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
Journal of Ovarian Research
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
url http://www.ovarianresearch.com/content/4/1/17
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AT shahparagp micrornasignatureofcisplatinresistantvscisplatinsensitiveovariancancercelllines
AT raisheshn micrornasignatureofcisplatinresistantvscisplatinsensitiveovariancancercelllines
AT pangulurisivak micrornasignatureofcisplatinresistantvscisplatinsensitiveovariancancercelllines
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