Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer
Most patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2402 |
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| author | Hui-Ching Wang Leong-Perng Chan Chun-Chieh Wu Shu-Jyuan Chang Sin-Hua Moi Chi-Wen Luo Mei-Ren Pan |
| author_facet | Hui-Ching Wang Leong-Perng Chan Chun-Chieh Wu Shu-Jyuan Chang Sin-Hua Moi Chi-Wen Luo Mei-Ren Pan |
| author_sort | Hui-Ching Wang |
| collection | DOAJ |
| description | Most patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly associated with carcinogenesis and treatment outcomes in oral squamous cell cancer, affecting cell growth and proliferation. Therefore, focusing on DNA repair and genetic instability interactions could be a potential target for improving the outcomes of OSCC patients. DNA polymerase-β (POLB) is an important enzyme in base excision repair and contributes to gene instability, leading to tumorigenesis and cancer metastasis. The aim of our study was to confirm POLB regulates the growth of OSCC cells through modulation of cell cycle and chromosomal instability. We analyzed a tissue array from 133 OSCC patients and discovered that low POLB expression was associated with advanced tumor stage and poor overall survival. In multivariate Cox proportional hazards regression analysis, low POLB expression and advanced lymph node status were significantly associated with poor survival. By performing in vitro studies on model cell lines, we demonstrated that POLB silencing regulated cell cycles, exacerbated mitotic abnormalities and enhanced cell proliferation. After POLB depletion, OSCC cells showed chromosomal instability and aneuploidy. Thus, POLB is an important maintainer of karyotypic stability in OSCC cells. |
| first_indexed | 2024-03-09T06:15:18Z |
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| id | doaj.art-0b27ffde0c264e7c8fc4b563635b617d |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:15:18Z |
| publishDate | 2021-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0b27ffde0c264e7c8fc4b563635b617d2023-12-03T11:53:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225240210.3390/ijms22052402Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell CancerHui-Ching Wang0Leong-Perng Chan1Chun-Chieh Wu2Shu-Jyuan Chang3Sin-Hua Moi4Chi-Wen Luo5Mei-Ren Pan6Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanFaculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, No.1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung 84001, TaiwanDepartment of Surgery, Division of Breast Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanMost patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly associated with carcinogenesis and treatment outcomes in oral squamous cell cancer, affecting cell growth and proliferation. Therefore, focusing on DNA repair and genetic instability interactions could be a potential target for improving the outcomes of OSCC patients. DNA polymerase-β (POLB) is an important enzyme in base excision repair and contributes to gene instability, leading to tumorigenesis and cancer metastasis. The aim of our study was to confirm POLB regulates the growth of OSCC cells through modulation of cell cycle and chromosomal instability. We analyzed a tissue array from 133 OSCC patients and discovered that low POLB expression was associated with advanced tumor stage and poor overall survival. In multivariate Cox proportional hazards regression analysis, low POLB expression and advanced lymph node status were significantly associated with poor survival. By performing in vitro studies on model cell lines, we demonstrated that POLB silencing regulated cell cycles, exacerbated mitotic abnormalities and enhanced cell proliferation. After POLB depletion, OSCC cells showed chromosomal instability and aneuploidy. Thus, POLB is an important maintainer of karyotypic stability in OSCC cells.https://www.mdpi.com/1422-0067/22/5/2402oral cancerDNA polymerase βcell cyclesaneuploidy |
| spellingShingle | Hui-Ching Wang Leong-Perng Chan Chun-Chieh Wu Shu-Jyuan Chang Sin-Hua Moi Chi-Wen Luo Mei-Ren Pan Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer International Journal of Molecular Sciences oral cancer DNA polymerase β cell cycles aneuploidy |
| title | Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer |
| title_full | Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer |
| title_fullStr | Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer |
| title_full_unstemmed | Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer |
| title_short | Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer |
| title_sort | silencing dna polymerase β induces aneuploidy as a biomarker of poor prognosis in oral squamous cell cancer |
| topic | oral cancer DNA polymerase β cell cycles aneuploidy |
| url | https://www.mdpi.com/1422-0067/22/5/2402 |
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