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Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer

  • Authors:
    • Zhengang Duan
    • Lei Cai
    • Jin Cao
    • Wei Wu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The 986 Air Force Hospital, Xi'an, Shaanxi 710000, P.R. China, Department of Digestive Surgery, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, P.R. China, Department of Endocrinology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, P.R. China, Department of Gastroenterology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, P.R. China
    Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 269
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    Published online on: June 20, 2022
       https://doi.org/10.3892/ol.2022.13389
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Abstract

High expression of polo‑like kinase 4 (PLK4) promotes tumorigenesis and is correlated with poor prognosis in several kinds of cancer. However, the prognostic value of PLK4 in colorectal cancer (CRC) has not been elucidated. The aim of the present study was to investigate the association between PLK4 and the prognosis and effect of PLK4 inhibition on chemosensitivity in CRC. A total of 142 patients with CRC were enrolled, and 142 pairs of CRC and para‑carcinoma tissues were used to measure PLK4 protein expression using immunohistochemistry (IHC). Among them, 69 pairs were used to detect PLK4 mRNA expression using reverse transcription‑quantitative PCR. In addition, PLK4‑small interfering RNA (siRNA) was transfected into CRC cells, followed by 5‑fluorouracil (5‑FU) treatment for it was a fundamental chemotherapy for CRC. In addition, western blotting was used to detect PLK4 protein expression among human colonic epithelial cell and human CRC cell lines, including HCT‑116, LoVo, SW480 and HT‑29, as well as nuclear translocation of β‑catenin. The IHC score and mRNA expression of PLK4 were higher in CRC tissues compared with para‑carcinoma tissues (both P<0.001). Furthermore, the IHC score of tumor PLK4 was not correlated with pathological grade (P=0.585), T stage (P=0.357), N stage (P=0.107225) or tumor‑node‑metastasis (TNM) stage (P=0.093). The mRNA expression of tumor PLK4 was positively correlated with N stage (P=0.019) and TNM stage (P=0.004), but not with pathological grade (P=0.498) or T stage (P=0.112). Of note, the high protein expression of tumor PLK4 was an independent factor for poor overall survival (OS; P=0.048). In addition, PLK4 was elevated in CRC cell lines; PLK4‑siRNA reduced the 50% inhibitory concentration value of 5‑FU in HCT‑116 (4.4±0.1 µM vs. 7.6±1.4 µM) and LoVo cells (5.5±0.6 µM vs. 9.9±1.8 µM) (both P<0.05). Besides, PLK4‑siRNA decreased nuclear translocation of β‑catenin. In conclusion, the high expression of tumor PLK4 was associated with advanced TNM stage and shorter OS in patients with CRC. In addition, targeting PLK4 improved chemosensitivity in CRC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Duan Z, Cai L, Cao J and Wu W: Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer. Oncol Lett 24: 269, 2022.
APA
Duan, Z., Cai, L., Cao, J., & Wu, W. (2022). Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer. Oncology Letters, 24, 269. https://doi.org/10.3892/ol.2022.13389
MLA
Duan, Z., Cai, L., Cao, J., Wu, W."Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer". Oncology Letters 24.2 (2022): 269.
Chicago
Duan, Z., Cai, L., Cao, J., Wu, W."Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer". Oncology Letters 24, no. 2 (2022): 269. https://doi.org/10.3892/ol.2022.13389
Copy and paste a formatted citation
x
Spandidos Publications style
Duan Z, Cai L, Cao J and Wu W: Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer. Oncol Lett 24: 269, 2022.
APA
Duan, Z., Cai, L., Cao, J., & Wu, W. (2022). Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer. Oncology Letters, 24, 269. https://doi.org/10.3892/ol.2022.13389
MLA
Duan, Z., Cai, L., Cao, J., Wu, W."Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer". Oncology Letters 24.2 (2022): 269.
Chicago
Duan, Z., Cai, L., Cao, J., Wu, W."Polo‑like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer". Oncology Letters 24, no. 2 (2022): 269. https://doi.org/10.3892/ol.2022.13389
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