Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells
The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects throu...
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MDPI AG
2023-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/20/2506 |
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| author | Tzitzijanik Madrigal Daniel Ortega-Bernal Luis A. Herrera Claudia Haydée González-De la Rosa Guadalupe Domínguez-Gómez Elena Aréchaga-Ocampo José Díaz-Chávez |
| author_facet | Tzitzijanik Madrigal Daniel Ortega-Bernal Luis A. Herrera Claudia Haydée González-De la Rosa Guadalupe Domínguez-Gómez Elena Aréchaga-Ocampo José Díaz-Chávez |
| author_sort | Tzitzijanik Madrigal |
| collection | DOAJ |
| description | The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model. |
| first_indexed | 2024-03-10T21:21:17Z |
| format | Article |
| id | doaj.art-18757587db7a42439f18fc47371b8216 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:21:17Z |
| publishDate | 2023-10-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-18757587db7a42439f18fc47371b82162023-11-19T16:03:08ZengMDPI AGCells2073-44092023-10-011220250610.3390/cells12202506Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer CellsTzitzijanik Madrigal0Daniel Ortega-Bernal1Luis A. Herrera2Claudia Haydée González-De la Rosa3Guadalupe Domínguez-Gómez4Elena Aréchaga-Ocampo5José Díaz-Chávez6Unidad de Investigación en Cáncer, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, San Fernando 22, Sección XVI, Tlalpan, CDMX, Mexico City 14080, MexicoDepartamento de Atención a la Salud, UAM Xochimilco, Mexico City 04960, MexicoUnidad de Investigación en Cáncer, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, San Fernando 22, Sección XVI, Tlalpan, CDMX, Mexico City 14080, MexicoDepartamento de Ciencias Naturales, Unidad Cuajimalpa, Universidad Autonóma Metropolitana, Mexico City 05348, MexicoSubdirección de Investigación Clínica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoDepartamento de Ciencias Naturales, Unidad Cuajimalpa, Universidad Autonóma Metropolitana, Mexico City 05348, MexicoUnidad de Investigación en Cáncer, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Instituto Nacional de Cancerología, San Fernando 22, Sección XVI, Tlalpan, CDMX, Mexico City 14080, MexicoThe master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model.https://www.mdpi.com/2073-4409/12/20/2506miRNAsmutant p53gain of functioncancer |
| spellingShingle | Tzitzijanik Madrigal Daniel Ortega-Bernal Luis A. Herrera Claudia Haydée González-De la Rosa Guadalupe Domínguez-Gómez Elena Aréchaga-Ocampo José Díaz-Chávez Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells Cells miRNAs mutant p53 gain of function cancer |
| title | Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells |
| title_full | Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells |
| title_fullStr | Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells |
| title_full_unstemmed | Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells |
| title_short | Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells |
| title_sort | mutant p53 gain of function induces migration and invasion through overexpression of mir 182 5p in cancer cells |
| topic | miRNAs mutant p53 gain of function cancer |
| url | https://www.mdpi.com/2073-4409/12/20/2506 |
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