Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment
Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3581 |
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| author | Irene Marchesi Milena Fais Francesco Paolo Fiorentino Valentina Bordoni Luca Sanna Stefano Zoroddu Luigi Bagella |
| author_facet | Irene Marchesi Milena Fais Francesco Paolo Fiorentino Valentina Bordoni Luca Sanna Stefano Zoroddu Luigi Bagella |
| author_sort | Irene Marchesi |
| collection | DOAJ |
| description | Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs. |
| first_indexed | 2024-03-09T11:47:20Z |
| format | Article |
| id | doaj.art-42d89446ade6482dbe59bd76f3679868 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:47:20Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-42d89446ade6482dbe59bd76f36798682023-11-30T23:19:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237358110.3390/ijms23073581Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma TreatmentIrene Marchesi0Milena Fais1Francesco Paolo Fiorentino2Valentina Bordoni3Luca Sanna4Stefano Zoroddu5Luigi Bagella6Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, ItalyRhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.https://www.mdpi.com/1422-0067/23/7/3581BET inhibitionrhabdomyosarcomaMYCBRD4(+)-JQ1 |
| spellingShingle | Irene Marchesi Milena Fais Francesco Paolo Fiorentino Valentina Bordoni Luca Sanna Stefano Zoroddu Luigi Bagella Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment International Journal of Molecular Sciences BET inhibition rhabdomyosarcoma MYC BRD4 (+)-JQ1 |
| title | Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment |
| title_full | Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment |
| title_fullStr | Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment |
| title_full_unstemmed | Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment |
| title_short | Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment |
| title_sort | bromodomain inhibitor jq1 provides novel insights and perspectives in rhabdomyosarcoma treatment |
| topic | BET inhibition rhabdomyosarcoma MYC BRD4 (+)-JQ1 |
| url | https://www.mdpi.com/1422-0067/23/7/3581 |
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