Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in va...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/8/1117 |
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| author | Yih-Gang Goan Pei-Feng Liu Hsueh-Wei Chang Hung-Chih Chen Wen-Chi Chen Shyh-Ming Kuo Cheng-Hsin Lee Chih-Wen Shu |
| author_facet | Yih-Gang Goan Pei-Feng Liu Hsueh-Wei Chang Hung-Chih Chen Wen-Chi Chen Shyh-Ming Kuo Cheng-Hsin Lee Chih-Wen Shu |
| author_sort | Yih-Gang Goan |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in various types of cancer. However, little is known about the role of kinases in OSCC cells. In this study, an arrayed kinome small interfering RNA (siRNA) library was used to screen oral cancer cell lines and counter assayed with normal fibroblast cells to identify the genes required for cancer cell proliferation. We found that polo-like kinase 1 (<i>PLK1</i>) was one of the most potent genes required for OSCC cell proliferation. The knockdown of <i>PLK1</i> with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G<sub>2</sub>-M phase transition. Similar effects were observed in cells treated with the PLK1 kinase inhibitor BI6727. Besides, The Cancer Genome Atlas (TCGA) analysis revealed that <i>PLK1</i> was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that <i>PLK1</i> expression was highly correlated with the expression of its downstream effector, CCNB1, in patients with OSCC. Coexpression of the two genes resulted in a poor prognosis of OSCC patients, particularly those in the advanced stages of OSCC. Taken together, our results suggest that <i>PLK1</i> might be a diagnostic or therapeutic marker for OSCC. |
| first_indexed | 2024-03-12T07:07:33Z |
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| id | doaj.art-d4b74d9879404666a34e8d047a50bc6e |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:07:33Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
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| series | Cancers |
| spelling | doaj.art-d4b74d9879404666a34e8d047a50bc6e2023-09-02T23:21:32ZengMDPI AGCancers2072-66942019-08-01118111710.3390/cancers11081117cancers11081117Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer CellsYih-Gang Goan0Pei-Feng Liu1Hsueh-Wei Chang2Hung-Chih Chen3Wen-Chi Chen4Shyh-Ming Kuo5Cheng-Hsin Lee6Chih-Wen Shu7Department of Surgery, Kaohsiung Veterans General Hospital Pingtung Branch, Pingtung 91245, TaiwanDepartment of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDivision of Oral & Maxillary Surgery, Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, TaiwanDepartment of Biomedical Engineering, I-Shou University, Kaohsiung 82445, TaiwanDivision of Oral & Maxillary Surgery, Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, TaiwanSchool of Medicine for International Students, I-Shou University, Kaohsiung 82445, TaiwanOral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in various types of cancer. However, little is known about the role of kinases in OSCC cells. In this study, an arrayed kinome small interfering RNA (siRNA) library was used to screen oral cancer cell lines and counter assayed with normal fibroblast cells to identify the genes required for cancer cell proliferation. We found that polo-like kinase 1 (<i>PLK1</i>) was one of the most potent genes required for OSCC cell proliferation. The knockdown of <i>PLK1</i> with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G<sub>2</sub>-M phase transition. Similar effects were observed in cells treated with the PLK1 kinase inhibitor BI6727. Besides, The Cancer Genome Atlas (TCGA) analysis revealed that <i>PLK1</i> was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that <i>PLK1</i> expression was highly correlated with the expression of its downstream effector, CCNB1, in patients with OSCC. Coexpression of the two genes resulted in a poor prognosis of OSCC patients, particularly those in the advanced stages of OSCC. Taken together, our results suggest that <i>PLK1</i> might be a diagnostic or therapeutic marker for OSCC.https://www.mdpi.com/2072-6694/11/8/1117kinomesiRNA screening<i>PLK1</i>oral squamous cell carcinomaprognosisbiomarker |
| spellingShingle | Yih-Gang Goan Pei-Feng Liu Hsueh-Wei Chang Hung-Chih Chen Wen-Chi Chen Shyh-Ming Kuo Cheng-Hsin Lee Chih-Wen Shu Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells Cancers kinome siRNA screening <i>PLK1</i> oral squamous cell carcinoma prognosis biomarker |
| title | Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells |
| title_full | Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells |
| title_fullStr | Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells |
| title_full_unstemmed | Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells |
| title_short | Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells |
| title_sort | kinome wide screening with small interfering rna identified polo like kinase 1 as a key regulator of proliferation in oral cancer cells |
| topic | kinome siRNA screening <i>PLK1</i> oral squamous cell carcinoma prognosis biomarker |
| url | https://www.mdpi.com/2072-6694/11/8/1117 |
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