Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer
Prostate cancer is a common carcinoma in males, the development of which involves the androgen receptor (AR) as a key regulator. AR transactivation induces the high expression of androgen-regulated genes, including transmembrane protease serine 2 (<i>TMPRSS2</i>) and long noncoding RNA p...
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2019-08-01
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| Series: | Cells |
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| author | Zikai Chen Xuhong Song Qidong Li Lingzhu Xie Tangfei Guo Ting Su Chang Tang Xiaolan Chang Bin Liang Dongyang Huang |
| author_facet | Zikai Chen Xuhong Song Qidong Li Lingzhu Xie Tangfei Guo Ting Su Chang Tang Xiaolan Chang Bin Liang Dongyang Huang |
| author_sort | Zikai Chen |
| collection | DOAJ |
| description | Prostate cancer is a common carcinoma in males, the development of which involves the androgen receptor (AR) as a key regulator. AR transactivation induces the high expression of androgen-regulated genes, including transmembrane protease serine 2 (<i>TMPRSS2</i>) and long noncoding RNA prostate cancer-associated transcript 38 (<i>PRCAT38</i>). <i>PRCAT38</i> and <i>TMPRSS2</i> are both located on chromosome 21, separated by a series of enhancers. <i>PRCAT38</i> is a prostate-specific long noncoding RNA that is highly expressed in cancer tissue as compared to normal tissue. Here, we show chromatin looping by enhancers E1 and E2 with the promoters for <i>PRCAT38</i> and <i>TMPRSS2</i>, indicating the co-regulation of <i>PRCAT38</i> and <i>TMPRSS2</i> by the same enhancers. The knockout of enhancer E1 or E2 simultaneously impaired the transcription of <i>PRCAT38</i> and <i>TMPRSS2</i> and inhibited cell growth and migration. Moreover, the loop formation and enhancer activity were mediated by AR/FOXA1 binding and the activity of acetyltransferase p300. Our findings demonstrate the utilization of shared enhancers in the joint regulation of two oncogenes in prostate cancer cells. |
| first_indexed | 2024-03-12T19:51:20Z |
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| language | English |
| last_indexed | 2024-03-12T19:51:20Z |
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| spelling | doaj.art-b8841ea7e4cc49b5b912882c6b8145772023-08-02T03:11:57ZengMDPI AGCells2073-44092019-08-018886410.3390/cells8080864cells8080864Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate CancerZikai Chen0Xuhong Song1Qidong Li2Lingzhu Xie3Tangfei Guo4Ting Su5Chang Tang6Xiaolan Chang7Bin Liang8Dongyang Huang9Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaDepartment of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, ChinaProstate cancer is a common carcinoma in males, the development of which involves the androgen receptor (AR) as a key regulator. AR transactivation induces the high expression of androgen-regulated genes, including transmembrane protease serine 2 (<i>TMPRSS2</i>) and long noncoding RNA prostate cancer-associated transcript 38 (<i>PRCAT38</i>). <i>PRCAT38</i> and <i>TMPRSS2</i> are both located on chromosome 21, separated by a series of enhancers. <i>PRCAT38</i> is a prostate-specific long noncoding RNA that is highly expressed in cancer tissue as compared to normal tissue. Here, we show chromatin looping by enhancers E1 and E2 with the promoters for <i>PRCAT38</i> and <i>TMPRSS2</i>, indicating the co-regulation of <i>PRCAT38</i> and <i>TMPRSS2</i> by the same enhancers. The knockout of enhancer E1 or E2 simultaneously impaired the transcription of <i>PRCAT38</i> and <i>TMPRSS2</i> and inhibited cell growth and migration. Moreover, the loop formation and enhancer activity were mediated by AR/FOXA1 binding and the activity of acetyltransferase p300. Our findings demonstrate the utilization of shared enhancers in the joint regulation of two oncogenes in prostate cancer cells.https://www.mdpi.com/2073-4409/8/8/864<i>TMPRSS2</i><i>PRCAT38</i>enhancerchromatin looping |
| spellingShingle | Zikai Chen Xuhong Song Qidong Li Lingzhu Xie Tangfei Guo Ting Su Chang Tang Xiaolan Chang Bin Liang Dongyang Huang Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer Cells <i>TMPRSS2</i> <i>PRCAT38</i> enhancer chromatin looping |
| title | Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer |
| title_full | Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer |
| title_fullStr | Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer |
| title_full_unstemmed | Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer |
| title_short | Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene <i>TMPRSS2</i> and lncRNA <i>PRCAT38</i> in Prostate Cancer |
| title_sort | androgen receptor activated enhancers simultaneously regulate oncogene i tmprss2 i and lncrna i prcat38 i in prostate cancer |
| topic | <i>TMPRSS2</i> <i>PRCAT38</i> enhancer chromatin looping |
| url | https://www.mdpi.com/2073-4409/8/8/864 |
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