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...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central Ltd.
2011
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| Online Access: | http://hdl.handle.net/1721.1/67286 |
| _version_ | 1826196381644095488 |
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| author | Kumar, Smriti R. Kumar, Arooshi R. Shah, Parag P. Rai, Shesh N. Panguluri, Siva K. Kakar, Sham S. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Kumar, Smriti R. Kumar, Arooshi R. Shah, Parag P. Rai, Shesh N. Panguluri, Siva K. Kakar, Sham S. |
| author_sort | Kumar, Smriti R. |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T10:25:59Z |
| format | Article |
| id | mit-1721.1/67286 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:25:59Z |
| publishDate | 2011 |
| publisher | BioMed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/672862022-09-26T17:51:03Z MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines Kumar, Smriti R. Kumar, Arooshi R. Shah, Parag P. Rai, Shesh N. Panguluri, Siva K. Kakar, Sham S. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Kumar, Smriti R. Kumar, Smriti R. Kumar, Arooshi R. 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. National Institutes of Health (U.S.) (NIH/NCI CA124630) 2011-11-21T22:12:07Z 2011-11-21T22:12:07Z 2011-09 2011-11-02T06:10:09Z Article http://purl.org/eprint/type/JournalArticle 1757-2215 http://hdl.handle.net/1721.1/67286 Kumar, Smriti et al. “MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines.” Journal of Ovarian Research. 2011 Sep 22;4(1):17. en http://dx.doi.org/10.1186/1757-2215-4-17 Journal of Ovarian Research Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Kumar et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd. BioMed Central Ltd |
| spellingShingle | Kumar, Smriti R. Kumar, Arooshi R. 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 |
| url | http://hdl.handle.net/1721.1/67286 |
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