A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes
Recent high-throughput-sequencing of the cancer genome has identified oncogenic mutations in BRaf genetic locus as one of the critical events in melanomagenesis. In normal cells, the activity of BRaf is tightly regulated. Gain-of-function mutations like those identified in melanoma frequently lead t...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/913242 |
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| author | Gang Ren Jingwei Feng Ila Datar Aaron H. Yeung Srinivas Vinod Saladi Yongqing Feng Ivana de la Serna Kam C. Yeung |
| author_facet | Gang Ren Jingwei Feng Ila Datar Aaron H. Yeung Srinivas Vinod Saladi Yongqing Feng Ivana de la Serna Kam C. Yeung |
| author_sort | Gang Ren |
| collection | DOAJ |
| description | Recent high-throughput-sequencing of the cancer genome has identified oncogenic mutations in BRaf genetic locus as one of the critical events in melanomagenesis. In normal cells, the activity of BRaf is tightly regulated. Gain-of-function mutations like those identified in melanoma frequently lead to enhanced cell-survival and unrestrained growth. The activating mutation of BRaf will also induce the cells to senesce. However, the mechanism by which the oncogenic BRaf induces the senescent barrier remains poorly defined. microRNAs have regulatory functions toward the expression of genes that are important in carcinogenesis. Here we show that expression of several microRNAs is altered when the oncogenic version of BRaf is introduced in cultured primary melanocytes and these cells undergo premature cellular senescence. These include eight microRNAs whose expression rates are significantly stimulated and three that are repressed. While most of the induced microRNAs have documented negative effects on cell cycle progression, one of the repressed microRNAs has proven oncogenic functions. Ectopic expression of some of these induced microRNAs increased the expression of senescence markers and induced growth arrest and senescence in primary melanocytes. Taken together, our results suggest that the change in microRNA expression rates may play a vital role in senescence induced by the oncogenic BRaf. |
| format | Article |
| id | doaj-art-2f2db51067aa47a8b91386c478377af3 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-2f2db51067aa47a8b91386c478377af32025-02-03T06:44:36ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/913242913242A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human MelanocytesGang Ren0Jingwei Feng1Ila Datar2Aaron H. Yeung3Srinivas Vinod Saladi4Yongqing Feng5Ivana de la Serna6Kam C. Yeung7Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USADepartment of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614-2598, USARecent high-throughput-sequencing of the cancer genome has identified oncogenic mutations in BRaf genetic locus as one of the critical events in melanomagenesis. In normal cells, the activity of BRaf is tightly regulated. Gain-of-function mutations like those identified in melanoma frequently lead to enhanced cell-survival and unrestrained growth. The activating mutation of BRaf will also induce the cells to senesce. However, the mechanism by which the oncogenic BRaf induces the senescent barrier remains poorly defined. microRNAs have regulatory functions toward the expression of genes that are important in carcinogenesis. Here we show that expression of several microRNAs is altered when the oncogenic version of BRaf is introduced in cultured primary melanocytes and these cells undergo premature cellular senescence. These include eight microRNAs whose expression rates are significantly stimulated and three that are repressed. While most of the induced microRNAs have documented negative effects on cell cycle progression, one of the repressed microRNAs has proven oncogenic functions. Ectopic expression of some of these induced microRNAs increased the expression of senescence markers and induced growth arrest and senescence in primary melanocytes. Taken together, our results suggest that the change in microRNA expression rates may play a vital role in senescence induced by the oncogenic BRaf.http://dx.doi.org/10.1155/2012/913242 |
| spellingShingle | Gang Ren Jingwei Feng Ila Datar Aaron H. Yeung Srinivas Vinod Saladi Yongqing Feng Ivana de la Serna Kam C. Yeung A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes International Journal of Cell Biology |
| title | A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes |
| title_full | A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes |
| title_fullStr | A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes |
| title_full_unstemmed | A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes |
| title_short | A Micro-RNA Connection in BRafV600E-Mediated Premature Senescence of Human Melanocytes |
| title_sort | micro rna connection in brafv600e mediated premature senescence of human melanocytes |
| url | http://dx.doi.org/10.1155/2012/913242 |
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