UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway

Wang,Kai; Tang,Jun; Liu,Xiaolei; Wang,Yuejian; Chen,Weixiong; Zheng,Rui

doi:10.3892/or.2020.7620

UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway

Authors:
- Kai Wang
- Jun Tang
- Xiaolei Liu
- Yuejian Wang
- Weixiong Chen
- Rui Zheng
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Affiliations: Department of Otorhinolaryngology‑Head and Neck Surgery, First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China, Department of Radiation Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Otorhinolaryngology‑Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: May 21, 2020 https://doi.org/10.3892/or.2020.7620
Pages: 685-697
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n‑recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non‑tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa‑PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5‑related lncRNA, targeted miRNA and protein‑protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen‑activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non‑tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si‑RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl‑2 and p38 was decreased in the si‑UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si‑UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5‑overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.

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