&lt;p&gt;DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1&lt;/p&gt;

Zhang, Chunlin; Mi, Jiaoping; Deng, Yuan; Deng, Zeyi; Long, Dan; Liu, Zhao-hui

doi:10.2147/ott.s227395

Cited by 9 publications

(14 citation statements)

References 42 publications

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“…Besides, there was a strong correlation between DGCR8 and hsa-miR-106a (Figure 2). As we have known in previous studies (22), HPV-positive HNSCC cells were highly sensitive to radiation, and HPV-positive cells were rich in DGCR8 and hsa-miR-106a. Ardenne and Reitnauer (27) demonstrated that hsa-miR-106a suppressed proliferation and induced apoptosis.…”

Section: Discussionsupporting

confidence: 56%

“…According to previous studies, we had proved that FaDu and UM-SCC-4 were HPV-negative cell lines and do not express HPV E7 proteins, while UM-SCC-090 and UM-SCC-47 were HPV-positive cell lines expressing E7 proteins (22). The mRNA ( Figure 1A) and protein ( Figure 1B) expressions of E7 in HPV-positive cell lines were higher than those of HPV-negative cell lines.…”

Section: Human Papillomavirus E7 Upregulates Dgcr8 Expression In Headmentioning

confidence: 70%

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DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3

et al. 2020

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Purpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant tumor worldwide, and the radiotherapy effect is strongly associated with human papillomavirus (HPV) infection. Therefore, the aim of our study was to analyze the mechanism of HPV E7 and its effects on radiosensitivity in HNSCC cells.Methods: The mRNA expression of DiGeorge syndrome critical region gene 8 (DGCR8), has-miR-106a, and Runt-related transcription factor 3 (RUNX3) was examined by quantitative real-time PCR (RT-qPCR). The protein expression of DGCR8, E7, RUNX3, caspase-3/cleaved caspase-3, poly(ADP-ribose) polymerase (PARP)/cleaved PARP, and γH2AX was measured by Western blot. The expression level of DGCR8 was measured by immunofluorescence assay. Starbase database (http://starbase.sysu.edu.cn/) was used to analyze the correlation between has-miR-106a-5p and DGCR8. TargetScan database (http://www.targetscan.org/vert_72/) was adopted to calculate the prediction of binding sites. Radiosensitivity was evaluated through clone formation assays and Cell Counting Kit-8 (CCK-8) assays.Results: In our study, we found that the mRNA and protein expression levels of HPV E7 and DGCR8 in HPV-positive HNSCC cells were higher than those in HPV-negative cells. The expression of DGCR8 was increased in FaDu and UM-SCC-4 with E7 overexpression, while the expression of DGCR8 was decreased in UM-SCC-47 and UPCI-SCC-090 with E7 silence. The miR-106a expression was increased after DGCR8 overexpression in FaDu and UM-SCC-4. However, the miR-106a expression was decreased in UM-SCC-47 and UPCI-SCC-090 with E7 silence. In radiation conditions, clone formation assays found that less clones formed in FaDu and UM-SCC-4 cells subsequent to silencing DGCR8 or miR-106a than that in the control group, and more clones were formed in UM-SCC-47 and UPCI-SCC-090 cells overexpressing DGCR8 or miR-106a than that in the control group. Luciferase reporter gene assays verified that miR-106a targeted the 3′ untranslated region (UTR) of RUNX3 mRNA. MiR-106a overexpression resulted in a decrease in RUNX3 expression, and miR-106a silence increased RUNX3 expression. Rescue experiments conducted with miR-106a inhibitor restored radiation resistance and reduced DNA damage in radiation condition.Conclusions: Our study indicated that HPV E7 activated DGCR8/miR-106a/RUNX3 axis to enhance radiation sensitivity and provided directions for targeted therapeutic interventions.

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Section: Discussionsupporting

confidence: 56%

Section: Human Papillomavirus E7 Upregulates Dgcr8 Expression In Headmentioning

confidence: 70%

DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3

et al. 2020

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“…DNMTs may be a potential target for enhancing HNSCC chemotherapy by using inhibitors of DNMTs and reversal of gene methylation [ 51 , 52 ]. It has been reported that DNMT1 enhances the radiosensitivity of neck squamous cell carcinomas via downregulating SMG1 [ 53 ]. The zinc finger protein 318 (encoded by the ZNF318 gene) was recognized previously as a blood pressure regulator [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

A SARS-CoV-2 –human metalloproteome interaction map

Chasapis

Georgiopoulou

Perlepes

et al. 2021

Journal of Inorganic Biochemistry

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The recent pandemic caused by the novel coronavirus resulted in the greatest global health crisis since the Spanish flu pandemic of 1918. There is limited knowledge of whether SARS-CoV-2 is physically associated with human metalloproteins. Recently, high-confidence, experimentally supported protein-protein interactions between SARS-CoV-2 and human proteins were reported. In this work, 58 metalloproteins among these human targets have been identified by a structure-based approach. This study reveals that most human metalloproteins interact with the recently discovered SARS-CoV-2 orf8 protein, whose antibodies are one of the principal markers of SARS-CoV-2 infections. Furthermore, this work provides sufficient evidence to conclude that Zn 2+ plays an important role in the interplay between the novel coronavirus and humans. First, the content of Zn-binding proteins in the involved human metalloproteome is significantly higher than that of the other metal ions. Second, a molecular linkage between the identified human Zn-binding proteome with underlying medical conditions that might increase the risk of severe illness from the SARS-CoV-2 virus has been found. Likely perturbations of host cellular metal homeostasis by SARS-CoV-2 infection are highlighted.

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“…For example, the levels of DNMT3B, NSUN2, DNMT3A, NOP2, DNMT1, NSUN4, NSUN5, and ALYREF were upregulated in lung adenocarcinoma (52). Zhang et al (53) have found that DNMT1 could enhance the radiosensitivity of HPV-positive HNSCC through suppressor of morphogenesis in genitalia 1 (SMG1). The NSUN family member, NSUN2, is found to be implicated in regulating cell cycles and accumulates in a variety of tumor lesions compared with normal samples (25,54).…”

Section: Discussionmentioning

confidence: 99%

Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

et al. 2021

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5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.

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

Cited by 9 publications

References 42 publications

DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3

DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3

A SARS-CoV-2 –human metalloproteome interaction map

Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

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