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Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells

1
Department of Surgery, Kaohsiung Veterans General Hospital Pingtung Branch, Pingtung 91245, Taiwan
2
Department of Nursing, Meiho University, Pingtung 91202, Taiwan
3
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
4
Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Division of Oral & Maxillary Surgery, Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
7
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
8
School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
9
Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan
10
School of Medicine for International Students, I-Shou University, Kaohsiung 82445, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1117; https://doi.org/10.3390/cancers11081117
Received: 22 July 2019 / Revised: 2 August 2019 / Accepted: 2 August 2019 / Published: 5 August 2019
(This article belongs to the Collection Cancer Biomarkers)
PDF [1984 KB, uploaded 5 August 2019]

Abstract

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 (PLK1) was one of the most potent genes required for OSCC cell proliferation. The knockdown of PLK1 with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G2-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 PLK1 was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that PLK1 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 PLK1 might be a diagnostic or therapeutic marker for OSCC.
Keywords: Kinome; siRNA screening; PLK1; oral squamous cell carcinoma; prognosis; biomarker Kinome; siRNA screening; PLK1; oral squamous cell carcinoma; prognosis; biomarker
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Goan, Y.-G.; Liu, P.-F.; Chang, H.-W.; Chen, H.-C.; Chen, W.-C.; Kuo, S.-M.; Lee, C.-H.; Shu, C.-W. Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells. Cancers 2019, 11, 1117.

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