Am J Otolaryngol Head Neck Surg | Volume 2, Issue 10 | Research Article | Open Access

Knockdown of UBR5 Chemosensitizers Human Laryngeal Carcinoma Cells In Vitro through Inhibition of NBS1

Xiaolei Liu1, Jun Tang2, Jingjia Li2, Youmou Chen3, Yuejian Wang2, Weixiong Chen2 and Kai Wang2*

1Department of Radiation Oncology, Beijing Shijitan Hospital, China
2Department of Otolaryngology, First People's Hospital of Foshan, China
3Department of Otolaryngology, Zunyi Medical University, China

*Correspondance to: Kai Wang 

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Abstract

Background: Laryngeal cancer is a common malignant tumor with low chemosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n-recognin 5 (UBR5) correlated with prognostic implications in many neoplasm's, while its role in laryngeal cancer remains to be elucidated. Methods: Immunohistochemistry was performed to measure UBR5 expression in laryngeal cancer and adjacent normal tissues. Differential transcriptional and protein expression were measured using Real-time PCR and Western Blot. The UBR5 gene was silenced with small interfere RNA in laryngeal cancer cells. In addition, proliferation and apoptosis level were measured using MTS assay and flow cytometry. Immunofluorescence was used to analyze DNA damage of UBR5 silencing laryngeal cancer cell induced by chemotherapy. Results: Elevated UBR5 expression is found in laryngeal cancer tissues compared with adjacent normal tissues. After silencing UBR5, cell proliferation and growth in vitro were significantly suppressed compared to the control group. In addition, chemotherapy efficiency in control cells showed a significantly higher in vitro proliferation rate than si-UBR5 cells. Mre11 complex subunit protein NBS1 was slightly downgraded after interference with UBR5, while expression level significantly increased after chemotherapy drug process. Silencing or treated with cisplatin (DDP) did not elevate the expression of γ-H2AX in laryngeal cancer cell, while combining UBR5 silencing with DDP treatment significantly increase γ-H2AX expression. Conclusion: our study has shown that UBR5 is highly expressed in laryngeal carcinoma tissues, and that down-regulation of UBR5 in laryngeal carcinoma cells may reduce sensitivity to chemotherapy. Together, these findings demonstrate that UBR5 plays a role in regulating sensitivity to chemotherapy in laryngeal cancer, and therefore highlight possible avenues for the development of new therapeutic strategies and targets for the treatment of this disease.

Keywords:

UBR5; Laryngeal cancer; Chemosensitivity; DNA damage; Apoptosis

Citation:

Liu X, Tang J, Li J, Chen Y, Wang Y, Chen W, et al. Knockdown of UBR5 Chemosensitizers Human Laryngeal Carcinoma Cells In Vitro through Inhibition of NBS1. Am J Otolaryngol Head Neck Surg. 2019;2(10):1079.

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