Cargando…
Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma
Genomic instability (GIN) plays a key role in cancer progression. The disorders of polymerase theta (POLQ) were reported to contribute to GIN and progression in many cancers. Here, we found that POLQ over‐expression was related to salivary adenoid cystic carcinoma (SACC) progression and poor prognos...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279586/ https://www.ncbi.nlm.nih.gov/pubmed/35726713 http://dx.doi.org/10.1111/jcmm.17429 |
_version_ | 1784746430488903680 |
---|---|
author | Bai, Han Xia, Shilin Zhu, Lei Dong, Yan Liu, Chao Li, Nan Liu, Han Xiao, Jing |
author_facet | Bai, Han Xia, Shilin Zhu, Lei Dong, Yan Liu, Chao Li, Nan Liu, Han Xiao, Jing |
author_sort | Bai, Han |
collection | PubMed |
description | Genomic instability (GIN) plays a key role in cancer progression. The disorders of polymerase theta (POLQ) were reported to contribute to GIN and progression in many cancers. Here, we found that POLQ over‐expression was related to salivary adenoid cystic carcinoma (SACC) progression and poor prognosis. Then, we investigated the role and mechanism of POLQ in the GIN in SACC. GIN was assessed by chromosome staining with DAPI and Giemsa, as well as qRT‐PCR of the mitosis‐related gene expression. Meanwhile, PCR‐SSCP was used to evaluate microsatellite instability. Modulation of POLQ expression increased chromosomal instability and enhanced the sensitivity to etoposide without impacting microsatellite stability. Mechanistically, POLQ regulated genome stability by promoting the expression of the error‐prone alt‐NHEJ‐related protein PARP1, and down‐regulating c‐NHEJ‐ and HR‐related proteins KU70 and RAD51. In vitro CCK, Transwell assays and in vivo murine xenograft models indicated that the PARP inhibitor olaparib suppressed SACC growth in the case of etoposide‐induced DNA damage. Bioinformatic analysis identified CEBPB as a potential POLQ‐regulating transcription factor. In summary, our research provides new insights into the mechanisms of SACC chromosomal instability and identifies new potential targets for SACC treatment. |
format | Online Article Text |
id | pubmed-9279586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92795862022-07-15 Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma Bai, Han Xia, Shilin Zhu, Lei Dong, Yan Liu, Chao Li, Nan Liu, Han Xiao, Jing J Cell Mol Med Original Articles Genomic instability (GIN) plays a key role in cancer progression. The disorders of polymerase theta (POLQ) were reported to contribute to GIN and progression in many cancers. Here, we found that POLQ over‐expression was related to salivary adenoid cystic carcinoma (SACC) progression and poor prognosis. Then, we investigated the role and mechanism of POLQ in the GIN in SACC. GIN was assessed by chromosome staining with DAPI and Giemsa, as well as qRT‐PCR of the mitosis‐related gene expression. Meanwhile, PCR‐SSCP was used to evaluate microsatellite instability. Modulation of POLQ expression increased chromosomal instability and enhanced the sensitivity to etoposide without impacting microsatellite stability. Mechanistically, POLQ regulated genome stability by promoting the expression of the error‐prone alt‐NHEJ‐related protein PARP1, and down‐regulating c‐NHEJ‐ and HR‐related proteins KU70 and RAD51. In vitro CCK, Transwell assays and in vivo murine xenograft models indicated that the PARP inhibitor olaparib suppressed SACC growth in the case of etoposide‐induced DNA damage. Bioinformatic analysis identified CEBPB as a potential POLQ‐regulating transcription factor. In summary, our research provides new insights into the mechanisms of SACC chromosomal instability and identifies new potential targets for SACC treatment. John Wiley and Sons Inc. 2022-06-21 2022-07 /pmc/articles/PMC9279586/ /pubmed/35726713 http://dx.doi.org/10.1111/jcmm.17429 Text en © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Bai, Han Xia, Shilin Zhu, Lei Dong, Yan Liu, Chao Li, Nan Liu, Han Xiao, Jing Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title | Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title_full | Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title_fullStr | Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title_full_unstemmed | Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title_short | Altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
title_sort | altered polymerase theta expression promotes chromosomal instability in salivary adenoid cystic carcinoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279586/ https://www.ncbi.nlm.nih.gov/pubmed/35726713 http://dx.doi.org/10.1111/jcmm.17429 |
work_keys_str_mv | AT baihan alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT xiashilin alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT zhulei alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT dongyan alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT liuchao alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT linan alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT liuhan alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma AT xiaojing alteredpolymerasethetaexpressionpromoteschromosomalinstabilityinsalivaryadenoidcysticcarcinoma |