BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma
Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/7/1046 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850078207911395328 |
|---|---|
| author | Mercedes Olvera-Valencia Fernando Luna-Maldonado Joselyn Juarez-Reyes Alejandro Lopez-Saavedra Jossimar Coronel-Hernandez Oliver Millan-Catalan Daniel Guzman-Gomez Frida Rodríguez-Izquierdo Luis A. Herrera David Francisco Cantú-De León Carlos Perez-Plasencia Eloy-Andres Pérez-Yepez |
| author_facet | Mercedes Olvera-Valencia Fernando Luna-Maldonado Joselyn Juarez-Reyes Alejandro Lopez-Saavedra Jossimar Coronel-Hernandez Oliver Millan-Catalan Daniel Guzman-Gomez Frida Rodríguez-Izquierdo Luis A. Herrera David Francisco Cantú-De León Carlos Perez-Plasencia Eloy-Andres Pérez-Yepez |
| author_sort | Mercedes Olvera-Valencia |
| collection | DOAJ |
| description | Sarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, <i>BUB1</i> was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high <i>BUB1</i> expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas. |
| format | Article |
| id | doaj-art-d6c0a20bc9d94a7d98bcad95054a6530 |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-d6c0a20bc9d94a7d98bcad95054a65302025-08-20T02:45:37ZengMDPI AGBiomolecules2218-273X2025-07-01157104610.3390/biom15071046BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and LeiomyosarcomaMercedes Olvera-Valencia0Fernando Luna-Maldonado1Joselyn Juarez-Reyes2Alejandro Lopez-Saavedra3Jossimar Coronel-Hernandez4Oliver Millan-Catalan5Daniel Guzman-Gomez6Frida Rodríguez-Izquierdo7Luis A. Herrera8David Francisco Cantú-De León9Carlos Perez-Plasencia10Eloy-Andres Pérez-Yepez11Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del IPN, Guillermo Massieu Helguera #239 Fracc. La escalera, Ticoman 07320, Ciudad de Mexico, MexicoUnidad de Investigación Biomédica en Cáncer, Insituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, Mexico City 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoAdvanced Microscopy Applications Unit (ADMIRA)-Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoLADISER de Inmunología y Biología Molecular, Facultad de Ciencias Químicas, Universidad Veracruzana (UV), Prolongación de Oriente 6 #1009, Colonia Rafael Alvarado, Orizaba 94340, Veracruz, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoUnidad de Investigación Biomédica en Cáncer, Insituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, Mexico City 14080, MexicoClinical Research, Instituto Nacional de Cancerologia, San Fernando 22. Col. Sección XVI, Tlalpan, Ciudad de Mexico 14080, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoLaboratorio de Genómica, Instituto Nacional de Cancerología, San Fernando 22. Col. Sección XVI, Tlalpan 14080, Ciudad de Mexico, MexicoSarcomas are heterogeneous mesenchymal tumors, and their pharmacological treatment remains challenging due to the high toxicity and poor efficacy of current therapies. This study aimed to identify common overexpressed kinases in the four most frequent sarcoma subtypes to establish novel therapeutic targets. A bioinformatics approach using patient-derived gene expression data sets identified overexpressed kinases shared across these sarcoma types. Later, <i>BUB1</i> was determined as the kinase consistently overexpressed across the osteosarcoma, liposarcoma, leiomyosarcoma, and synovial sarcoma. Moreover, the role of this kinase was further validated through molecular and functional assays, including pharmacological inhibition in cell lines derived from the four sarcoma subtypes. BUB1 inhibition reduced the phosphorylation of AKT and H2A proteins, precluded cell proliferation, and inhibited colony formation in sarcoma cells. Finally, overall survival analysis highlighted a strong correlation between high <i>BUB1</i> expression and poorer survival rates in sarcoma patients. Altogether, these findings underscore the potential of BUB1 as a therapeutic target and prognostic marker in sarcomas. Targeted inhibition of BUB1 may provide a novel strategy to reduce tumor growth and improve outcomes for patients with bone and soft tissue sarcomas.https://www.mdpi.com/2218-273X/15/7/1046sarcomakinasesbone sarcomatherapeutic targetsoft tissue sarcomas |
| spellingShingle | Mercedes Olvera-Valencia Fernando Luna-Maldonado Joselyn Juarez-Reyes Alejandro Lopez-Saavedra Jossimar Coronel-Hernandez Oliver Millan-Catalan Daniel Guzman-Gomez Frida Rodríguez-Izquierdo Luis A. Herrera David Francisco Cantú-De León Carlos Perez-Plasencia Eloy-Andres Pérez-Yepez BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma Biomolecules sarcoma kinases bone sarcoma therapeutic target soft tissue sarcomas |
| title | BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma |
| title_full | BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma |
| title_fullStr | BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma |
| title_full_unstemmed | BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma |
| title_short | BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma |
| title_sort | bub1 an overexpressed kinase in sarcoma finding new target therapy for osteosarcoma liposarcoma synovial sarcoma and leiomyosarcoma |
| topic | sarcoma kinases bone sarcoma therapeutic target soft tissue sarcomas |
| url | https://www.mdpi.com/2218-273X/15/7/1046 |
| work_keys_str_mv | AT mercedesolveravalencia bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT fernandolunamaldonado bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT joselynjuarezreyes bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT alejandrolopezsaavedra bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT jossimarcoronelhernandez bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT olivermillancatalan bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT danielguzmangomez bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT fridarodriguezizquierdo bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT luisaherrera bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT davidfranciscocantudeleon bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT carlosperezplasencia bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma AT eloyandresperezyepez bub1anoverexpressedkinaseinsarcomafindingnewtargettherapyforosteosarcomaliposarcomasynovialsarcomaandleiomyosarcoma |