UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway
UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway
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DOI：
10.3892/or.2020.7620
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发表时间：
2020-08-01
期刊：
影响因子：
4.2
通讯作者：
Zheng, Rui
中科院分区：
文献类型：
--
作者：
Wang, Kai;Tang, Jun;Zheng, Rui
喉癌（LCC）是一种常见的恶性肿瘤，放射敏感性低，反应率一般较差。泛素蛋白连接酶E3组分n-识别蛋白5 （UBR5）在几种肿瘤中具有预后意义；然而，它在LCC和放疗敏感性中的作用尚不清楚。免疫组织化学和生物信息学分析检测了UBR5蛋白和mRNA在LCC和邻近非肿瘤组织中的表达。采用定量PCR和western blot方法检测LCC和HuLa-PC细胞株中UBR5基因和蛋白的表达。在LCC细胞中转染小干扰RNA或UBR5过表达质粒，分析LCC细胞的增殖、细胞周期分布、侵袭、迁移和放射敏感性。利用生物信息学分析了ubr5相关的lncRNA、靶向miRNA和蛋白-蛋白相互作用网络。最后，在辐射处理的M2E细胞中，UBR5沉默后，评估p38/丝裂原活化蛋白激酶（MAPK）通路的表达。与邻近非肿瘤组织相比，LCC组织中UBR5表达升高，并与LCC患者总生存率较低相关。UBR5在M2E和M4E LCC细胞中过表达或沉默后，与对照组相比，细胞增殖和放射敏感性分别显著增加或降低。与对照组相比，UBR5 si-RNA组S期细胞百分比下降，而UBR5过表达对细胞周期无影响。此外，si-UBR5联合放疗组Bcl-2和p38的表达降低。si-UBR5联合放疗后p38磷酸化表达水平升高。p38/MAPK信号的小分子抑制剂SB203580降低了ubr5过表达细胞的活力和细胞暴露于辐射时的存活分数。这些发现表明，UBR5可能通过p38/MAPK通路参与调节LCC细胞增殖和对放疗的敏感性，从而突出了其在开发新的治疗策略和治疗靶点方面的可能价值。
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.