OncoTargets and Therapy (May 2020)

DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1

  • Zhang C,
  • Mi J,
  • Deng Y,
  • Deng Z,
  • Long D,
  • Liu Z

Journal volume & issue
Vol. Volume 13
pp. 4201 – 4211

Abstract

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Chunlin Zhang,1,* Jiaoping Mi,2,* Yuan Deng,1 Zeyi Deng,3 Dan Long,1,4 Zhaohui Liu1 1Department of Otorhinolaryngology, Head and Neck Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-Sun University, Zunyi, People’s Republic of China; 3Department of Otorhinolaryngology, Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4The Graduate School of Zunyi Medical University, Zunyi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunlin Zhang; Zhaohui LiuDepartment of Otorhinolaryngology, Head and Neck Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of ChinaEmail [email protected]; [email protected]: Head 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.Methods: The 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.Results: In 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.Conclusion: Our study indicated that DNMT1 enhances the radiosensitivity of HPV-positive head and neck squamous cell carcinomas via downregulating SMG1.Keywords: head and neck cancer, HPV, DNMT1, SMG1, radiotherapy

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