Epigenetic regulation of VENTXP1 suppresses tumor proliferation via miR-205-5p/ANKRD2/NF-kB signaling in head and neck squamous cell carcinoma

Abstract An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in tumor development and progression. However, their involvement in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Epigenetic regulation is one major mechanism utilized by cancer cells to control lncRNA expression. We identified that lncRNA VENTXP1 was epigenetically silenced in multiple cancer types, and its lower expression was correlated with poorer survival in HNSCC patients. Through in silico analysis and experimental validation, we identified miR-205-5p and its direct interacting partner of VENTXP1, which regulates HNSCC cell proliferation and tumorigenicity. Using RNA-seq and differential gene expression analysis, we further identified ANKRD2 as a miR-205-5p target, which plays an essential role in modulating NF-kB signaling. These findings suggest that VENTXP1 inhibits tumor growth via suppressing miR-205-5p/ANKRD2-mediated NF-kB signaling in HNSCC. Thus, pharmaceutical targeting of DNA methylation to restore VENTXP1 expression might constitute a therapeutic strategy for HNSCC.

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Multi-Omics Integrative Analysis Identifying EPC1 as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma

10.21203/rs.3.rs-507801/v1 ◽

2021 ◽

Author(s):

Yongmei Dai ◽

Wenhan chen ◽

Junpeng Huang ◽

Tongjian Cui ◽

chen huang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Protective Factor ◽

Prognostic Significance ◽

Endocrine Resistance ◽

Neck Squamous Cell Carcinoma ◽

Multiple Cancer ◽

Patient Prognosis

Abstract Background: To investigate the prognostic significance and related mechanisms of the expression of enhancer of polycomb homolog 1 ( EPC1 ) in head and neck squamous cell carcinoma (HNSCC) from a multi-omics perspective. Methods: The Kaplan-Meier plotter was used to evaluate the prognostic significance of EPC1 . Based on the LinkedOmics, UALCAN, and Timer platforms, the multi-omics expression of EPC1 in HNSCC was explored to investigate mechanisms affecting prognoses. Results: At the genetic level, 8208 genes were negatively correlated with EPC1 expression, and 11,956 genes were positively correlated with EPC1 expression. For the noncoding region, a competing endogenous RNA (ceRNA) network was constructed, and 6 microRNAs (miRNAs) and 3 long noncoding RNAs (lncRNAs) were identified. At the protein level, a protein-protein interaction (PPI) network related to EPC1 expression was constructed and was involved in human papillomavirus (HPV) infection, endocrine resistance, and multiple cancer pathways. At the immune level, EPC1 expression was correlated with a variety of immune cells, immune molecules, and chemokine receptors, which together constitute the immune microenvironment of tumors. According to the clinical data, high EPC1 expression in HNSCC was a predictor of patient prognosis (hazard ratio (HR)=0.64; 95% confidence interval (CI) 0.49-0.83; P<0.01). EPC1 expression differentiated clinical subtypes and was related to key factors such as TP53 and HPV (P<0.05). Conclusion: High EPC1 expression is a protective factor in HNSCC and benefits patient survival. EPC1 may participate in the genomics, transcriptomics, proteomics, and immunomics of HNSCC, and the results can provide a reference for the development of targeted drugs and the evaluation of patient prognosis.

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Author Correction: NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-020-77481-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Eun Kyung Kim ◽

Yoon Ah Cho ◽

Mi-kyoung Seo ◽

Hyunmi Ryu ◽

Byoung Chul Cho ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Epigenetic Regulation ◽

Neck Squamous Cell Carcinoma

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22126199 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6199

Author(s):

Sachi Oshima ◽

Shunichi Asai ◽

Naohiko Seki ◽

Chikashi Minemura ◽

Takashi Kinoshita ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cox Regression ◽

In Silico Analysis ◽

Neck Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Oncogenic Potential ◽

Mirna Expression Signature

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.

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Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma

Frontiers in Pharmacology ◽

10.3389/fphar.2021.779779 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xing-xing Huo ◽

Shu-jie Wang ◽

Hang Song ◽

Ming-de Li ◽

Hua Yu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Rna Stability ◽

Tumor Development ◽

Alternative Polyadenylation ◽

Neck Squamous Cell Carcinoma ◽

Rna Modifications

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer malignancy worldwide and is known to have poor prognosis. The pathogenesis behind the development of HNSCC is not fully understood. Modifications on RNA are involved in many pathophysiological processes, such as tumor development and inflammation. Adenosine-related RNA modifications have shown to be linked to cancer and may play a role in cancer occurrence and development. To date, there are at least 170 different chemical RNA modifications that modify coding and non-coding RNAs (ncRNAs). These modifications affect RNA stability and transcription efficiency. In this review, we focus on the current understanding of the four major RNA adenosine modifications (N6-Methyladenosine, N1-Methyladenosine, Alternative Polyadenylation Modification and A-to-I RNA editing) and their potential molecular mechanisms related to HNSCC development and progression. We also touch on how these RNA modifications affect treatment of HNSCCs.

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In Silico analysis and linking of metabolism-related genes with the immune landscape in head and neck squamous cell carcinoma

BIOCELL ◽

10.32604/biocell.2022.016612 ◽

2022 ◽

Vol 46 (1) ◽

pp. 111-125

Author(s):

JIAYU ZHANG ◽

RUOYAN CAO ◽

JIANMIN PENG ◽

QINCHAO HU ◽

JUAN XIA ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

In Silico ◽

In Silico Analysis ◽

Neck Squamous Cell Carcinoma ◽

Silico Analysis

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Triggering of Toll-like Receptor 4 Expressed on Human Head and Neck Squamous Cell Carcinoma Promotes Tumor Development and Protects the Tumor from Immune Attack

Cancer Research ◽

10.1158/0008-5472.can-08-3838 ◽

2009 ◽

Vol 69 (7) ◽

pp. 3105-3113 ◽

Cited By ~ 153

Author(s):

Miroslaw J. Szczepanski ◽

Malgorzata Czystowska ◽

Marta Szajnik ◽

Malgorzata Harasymczuk ◽

Michael Boyiadzis ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Development ◽

Human Head ◽

Neck Squamous Cell Carcinoma ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Immune Attack

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Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20061520 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1520 ◽

Cited By ~ 13

Author(s):

Cristina Porcheri ◽

Christian Thomas Meisel ◽

Thimios Mitsiadis

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Development ◽

Notch Pathway ◽

Neck Squamous Cell Carcinoma ◽

Special Focus ◽

Upper Aerodigestive Tract

Head and neck squamous cell carcinoma (HNSCC) defines a group of solid tumors originating from the mucosa of the upper aerodigestive tract, pharynx, larynx, mouth, and nasal cavity. It has a metastatic evolution and poor prognosis and is the sixth most common cancer in the world, with 600,000 new cases reported every year. HNSCC heterogeneity and complexity is reflected in a multistep progression, involving crosstalk between several molecular pathways. The Notch pathway is associated with major events supporting cancerogenic evolution: cell proliferation, self-renewal, angiogenesis, and preservation of a pro-oncogenic microenvironment. Additionally, Notch is pivotal in tumor development and plays a dual role acting as both oncogene and tumor suppressor. In this review, we summarize the role of the Notch pathway in HNSCC, with a special focus on its compelling role in major events of tumor initiation and growth.

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