DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1
DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1
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DNMT1 通过下调 SMG1 增强 HPV 阳性头颈鳞状细胞癌的放射敏感性
DOI：
10.2147/ott.s227395
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Liu, Zhaohui
中科院分区：
文献类型：
--
作者：
Zhang, Chunlin;Mi, Jiaoping;Liu, Zhaohui
头颈部鳞状细胞癌（Head and neck squamous cell carcinoma，HNSCC）是世界上排名第7位的恶性肿瘤，其发生与甲基化和HPV感染密切相关。电离辐射治疗是晚期HNSCC的主要治疗策略。以前，HPV阳性的HNSCC在放疗下比HPV阴性的HNSCC预测更好的预后，但其分子机制尚未解决。方法采用qPCR和Western blot方法检测不同处理方法对HPV-E6/E7、p16、p53、DNMT 1、SMG 1基因mRNA和蛋白表达的影响。结果采用RT-qPCR和Western blot检测头颈癌细胞系中HPV 16 E6、DNA甲基转移酶1（DNMT 1）和SMG 1的表达。通过过表达质粒在HPV阴性细胞中强制E6水平促进DNMT 1的表达，从而导致SMG 1表达降低。沉默SMG 1在HPV阴性的HNSCC细胞引起放射敏感性增加，这表明SMG 1可能是一个有效的开关，以调节放疗在HNSCC.ConclusionOur研究表明，DNMT 1增强HPV阳性的头颈部鳞状细胞癌的放射敏感性通过下调SMG 1。
IntroductionHead and neck squamous cell carcinoma (HNSCC), which rank the 7th malignant tumors worldwide, is closely related to methylation and HPV infection. Ionizing radiation therapy is the main strategy for HNSCC patients in advanced stage. Previously, HPV-positive HNSCC predict better prognosis than HPV-negative HNSCCs under radiotherapy, however its molecular mechanism is unresolved. SMG1 serves as a potential tumor suppressor in various cancers, including HNSCC.MethodsThe mRNAs and proteins expression of HPV E6/E7, p16, p53, DNMT1, SMG1 were detected after different treatments by qPCR and Western blot. The clone formation ability was measured in radiation dose after different treatments.ResultsIn our study, the expression of HPV16 E6, DNA Methyltransferase 1(DNMT1) and SMG1 in head and neck carcinomas cell lines was detected by RT-qPCR and Western blot. Forced E6 level in HPV-negative cells by overexpression plasmid promoted the expression of DNMT1, which resulted in decreased SMG1 expression. Silenced SMG1 in HPV-negative HNSCC cells elicited increased radiation sensitivity, suggesting that SMG1 may be an effective switch to regulate the effect of radiotherapy in HNSCC.ConclusionOur study indicated that DNMT1 enhances the radiosensitivity of HPV-positive head and neck squamous cell carcinomas via downregulating SMG1.