scholarly journals HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Dan Long ◽  
Li Xu ◽  
Zeyi Deng ◽  
Dandan Guo ◽  
Yangchun Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Cancer Type ◽  
Luciferase Reporter Gene ◽  
Hpv16 E6

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignant cancer type worldwide. Radiosensitivity has been shown to be significantly increased in patients with human papillomavirus (HPV)-positive HNSCC compared with HPV-negative patients. However, the clinical significance of HPV and its regulatory mechanisms in HNSCC are largely unknown. The aim of our study was to explore the regulatory mechanism of miR-27a-3p in the radiosensitivity of HPV-positive HNSCC cells. Methods E6-overexpressing and E6-knockdown HNSCC cell lines were generated and the transfection efficiencies were evaluated by quantitative real-time PCR (RT-qPCR) and western blotting. The expression of miR-27a-3p and DiGeorge syndrome critical region 8 (DGCR8) was examined by RT-qPCR after transfection with E6 overexpressing plasmid or E6 siRNA. The effects of miR-27a-3p on the radiosensitivity of HNSCC cells were explored by a colony formation and TUNEL staining assays. Bioinformatic tools and luciferase reporter assays were used to identify that SMG1 is the direct target of miR-27a-3p. Furthermore, the effect of E6 overexpression on the regulation of the miR-27a-3p/SMG1 axis was investigated. Results In our study, we found overexpression of HPV E6 upregulated the expression of DGCR8 and miR-27a-3p in HNSCC cells. We next confirmed that DGCR8 positively regulated the expression of miR-27a-3p in HNSCC cells. The luciferase reporter gene results verified that miR-27a-3p targeted the 3’UTR of SMG1 mRNA. MiR-27a-3p mimics transfection resulted in a decrease in SMG1 expression and miR-27a-3p inhibitor transfection increased SMG1 expression. Apoptotic activity of HNSCC cells was significantly increased in miR-27a-3p mimics HNSCC cells compared with control HNSCC cells. After treatment with 4 Gy irradiation, UM-SCC47 cells transfected with miR-27a-3p inhibitor or SMG1 overexpressing plasmid formed more colonies than the corresponding control cells. Furthermore, the rescue experiments demonstrated that HPV16 E6 improved the radiosensitivity of HNSCC cells by targeting miR-27a-3p/SMG1. Conclusion Our study demonstrated that HPV16 E6 activated the DGCR8/miR-27a-3p/SMG1 axis to enhance the radiosensitivity. Our findings might provide a novel therapeutic target to improve the response of HNSCC to radiotherapy.

scholarly journals miR-18a-5p Facilitates Malignant Progression of Head and Neck Squamous Cell Carcinoma Cells via Modulating SORBS2

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qian Chen ◽  
Jing Xu ◽  
Mingzhen Zhu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

This study attempted to investigate possible molecular mechanism and role of miR-18a-5p in head and neck squamous cell carcinoma (HNSCC). Differential miRNAs and their possible targets were analyzed through TCGA database. By conducting qRT-PCR, miR-18a-5p was tested to be increased and SORBS2 was assessed to be downregulated in HNSCC cells. CCK-8, Transwell, and flow cytometry assays disclosed that miR-18a-5p facilitated HNSCC cell proliferation, migration, and invasion and repressed cell apoptosis. By dual-luciferase reporter gene assay, it was verified that miR-18a-5p had binding sites into SORBS2. Rescue experiments displayed that forced expression of SORBS2 restored the impact of miR-18a-5p overexpression on HNSCC cells. Collectively, our research preliminarily identified the promotion effect of miR-18a-5p/SORBS2 axis on malignant phenotypes of HNSCC cells. Our findings may provide a preclinical reference for HNSCC treatment.

scholarly journals CAFE MOCHA: An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer—An Example of Distant Metastasis– and Recurrence-Linked Classifiers in Head and Neck Squamous Cell Carcinoma

2018 ◽  
pp. 1-11
Author(s):  
Neeraja M. Krishnan ◽  
Mohanraj I ◽  
Janani Hariharan ◽  
Binay Panda
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
Cancer Type ◽  
Molecular Signatures ◽  
Molecular Changes ◽  
Statistical Framework

Purpose With large amounts of multidimensional molecular data on cancers generated and deposited into public repositories such as The Cancer Genome Atlas and International Cancer Genome Consortium, a cancer type agnostic and integrative platform will help to identify signatures with clinical relevance. We devised such a platform and showcase it by identifying a molecular signature for patients with metastatic and recurrent (MR) head and neck squamous cell carcinoma (HNSCC). Methods We devised a statistical framework accompanied by a graphical user interface–driven application, Clinical Association of Functionally Established MOlecular CHAnges ( CAFE MOCHA; https://github.com/binaypanda/CAFEMOCHA), to discover molecular signatures linked to a specific clinical attribute in a cancer type. The platform integrates mutations and indels, gene expression, DNA methylation, and copy number variations to discover a classifier first and then to predict an incoming tumor for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry–based algorithm called complete specificity margin-based clustering, which ensures maximum specificity. CAFE MOCHA classifies an incoming tumor sample using either its matched normal or a built-in database of normal tissues. The application is packed and deployed using the install4j multiplatform installer. We tested CAFE MOCHA in HNSCC tumors (n = 513) followed by validation in tumors from an independent cohort (n = 18) for discovering a signature linked to distant MR. Results CAFE MOCHA identified an integrated signature, MR44, associated with distant MR HNSCC, with 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage. Conclusion CAFE MOCHA is a cancer type and clinical attribute agnostic statistical framework to discover integrated molecular signatures.

scholarly journals Development of a Spontaneous HPV16 E6/E7-Expressing Head and Neck Squamous Cell Carcinoma in HLA-A2 Transgenic Mice

mBio ◽  
2022 ◽  
Author(s):  
Shiwen Peng ◽  
Deyin Xing ◽  
Louise Ferrall ◽  
Ya-Chea Tsai ◽  
Richard B. S. Roden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transgenic Mice ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Mhc I ◽  
Hpv16 E6 ◽  
E6 And E7

Our data indicate that mutated HPV16 E6(R55K)(delK75) and mutated HPV16 E7(N53S) DNA abolishes the presentation of HPV16 E6 and E7 through murine MHC-I and results in their presentation through human HLA-A2 molecules. Additionally, the mutated HPV16 E6 and E7 remain oncogenic.

scholarly journals HOXC6 Is Deregulated in Human Head and Neck Squamous Cell Carcinoma and Modulates Bcl-2 Expression

2012 ◽  
Vol 287 (42) ◽  
pp. 35678-35688 ◽  
Author(s):  
Sung-Min Moon ◽  
Soo-A Kim ◽  
Jung-Hoon Yoon ◽  
Sang-Gun Ahn
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Protein A ◽  
Human Head ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Apoptotic Pathway ◽  
Induced Apoptosis

Homeobox C6 (HOXC6) genes belong to the homeoprotein family of transcription factors, which play an important role in morphogenesis and cellular differentiation during embryonic development. The aim of this study was to explore the role of HOXC6 in the regulation of Bcl-2 in human head and neck squamous cell carcinoma (HNSCC). The HOXC6 and Bcl-2 gene were identified as being overexpressed in HNSCC tissue and cell lines. Transfection assays demonstrated that HOXC6 increased the levels of Bcl-2 mRNA and protein. A luciferase reporter assay suggested that HOXC6 induced activity of the Bcl-2 promoter. A series of Bcl-2 promoter deletion mutants were examined and the minimal HOXC6-responsive region was identified to be in the TAAT motif (-420 bp) of the Bcl-2 promoter. Interestingly, the inhibition of HOXC6 using siRNA led to the repression of Bcl-2 expression and induced caspase-3-dependent apoptosis; overexpression of HOXC6 in HNSCC cells increased the resistance to paclitaxel-induced apoptosis. Together, our findings suggest that HOXC6 is an important mechanism of the anti-apoptotic pathway via regulation of Bcl-2 expression.

Long noncoding RNA KTN1-AS1 promotes head and neck squamous cell carcinoma cell epithelial–mesenchymal transition by targeting miR-153-3p

Epigenomics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 487-505 ◽  
Author(s):  
Yingying Jiang ◽  
Kun Wu ◽  
Wei Cao ◽  
Qin Xu ◽  
Xu Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Mesenchymal Transition

Aim: To explore the biological functions and clinicopathologic significance of the long noncoding RNA KTN1-AS1 in head and neck squamous cell carcinoma (HNSCC). Materials & methods: We assessed the effects of KTN1-AS1 and identified the target miRNA by bioinformatics analysis, luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. The clinicopathologic features of KTN1-AS1 and its target miRNA were analyzed in HNSCC. Results: KTN1-AS1, a competing endogenous RNA, promoted cell proliferation, migration, invasion and epithelial–mesenchymal transition by sponging miR-153-3p in HNSCC. Dysregulation of SNAI1 and ZEB2 mediated the effect of KTN1-AS1 due to miR-153-3p exhaustion. The KTN1-AS1 and miR-153-3p combination can accurately diagnose HNSCC. Conclusion: The KTN1-AS1 and miR-153-3p combination could be a valuable diagnostic and prognostic predictor for HNSCC.

scholarly journals Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1018
Author(s):  
Florencia Veigas ◽  
Yamil D. Mahmoud ◽  
Joaquin Merlo ◽  
Adriana Rinflerch ◽  
Gabriel Adrian Rabinovich ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune System ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Predictive Biomarkers ◽  
Neck Squamous Cell Carcinoma ◽  
Cancer Type

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives.

scholarly journals Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (18) ◽  
pp. 9947
Author(s):  
Ayaka Koma ◽  
Shunichi Asai ◽  
Chikashi Minemura ◽  
Sachi Oshima ◽  
Takashi Kinoshita ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Biology ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Expression Levels ◽  
Passenger Strand

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.

scholarly journals Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1910
Author(s):  
Nozomi Tanaka ◽  
Chikashi Minemura ◽  
Shunichi Asai ◽  
Naoko Kikkawa ◽  
Takashi Kinoshita ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Cancer Pathogenesis

Our previous study revealed that the miR-199 family (miR-199a-5p/-3p and miR-199b-5p/-3p) acts as tumor-suppressive miRNAs in head and neck squamous cell carcinoma (HNSCC). Furthermore, recent studies have indicated that the passenger strands of miRNAs are involved in cancer pathogenesis. The aim of this study was to identify cancer-promoting genes commonly regulated by miR-199-5p and miR-199-3p in HNSCC cells. Our in silico analysis and luciferase reporter assay identified paxillin (PXN) as a direct target of both miR-199-5p and miR-199-3p in HNSCC cells. Analysis of the cancer genome atlas (TCGA) database showed that expression of PXN significantly predicted a worse prognosis (5-year overall survival rate; p = 0.0283). PXN expression was identified as an independent factor predicting patient survival according to multivariate Cox regression analyses (p = 0.0452). Overexpression of PXN was detected in HNSCC clinical specimens by immunostaining. Functional assays in HNSCC cells showed that knockdown of PXN expression attenuated cancer cell migration and invasion, suggesting that aberrant expression of PXN contributed to HNSCC cell aggressiveness. Our miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.

scholarly journals CAFE MOCHA:An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer; an Example of Distant Metastasis and Recurrence-linked Classifiers in Head and Neck Squamous Cell Carcinoma

2017 ◽  
Author(s):  
Neeraja M Krishnan ◽  
I Mohanraj ◽  
Janani Hariharan ◽  
Binay Panda
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Distant Metastasis ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Signature ◽  
Cancer Type ◽  
Molecular Changes ◽  
Statistical Framework

AbstractBackgroundCAFE MOCHA(Clinical Association of Functionally Established MOlecular CHAnges) is an integrated GUI-driven computational and statistical framework to discover molecular signatures linked to a specific clinical attribute in a cancer type. We testedCAFE MOCHAin head and neck squamous cell carcinoma (HNSCC) for discovering a signature linked to distant metastasis and recurrence (MR) in 517 tumors from TCGA and validated the signature in 18 tumors from an independent cohort.MethodsThe platform integrates mutations and indels, gene expression, DNA methylation and copy number variations to discover a classifier first, predict an incoming tumour for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry-based algorithm, called Complete Specificity Margin Based Clustering (CSMBC) with 100% specificity.CAFE MOCHAclassifies an incoming tumour sample using either a matched normal or a built-in database of normal tissues. The application is packed and deployed using theinstall4jmulti-platform installer.ResultsWe testedCAFE MOCHAto discover a signature for distant metastasis and recurrence in HNSCC. The signature MR44 in HNSCC yielded 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage.ConclusionsCAFE MOCHAis a cancer type- and clinical attribute-agnostic computational and statistical framework to discover integrated molecular signature for a specific clinical attribute.CAFE MOCHAis available in GitHub (https://github.com/binaypanda/CAFEMOCHA).

A novel mechanism of miRNA-mediated CBX8 associated with tumorigenesis in head and neck squamous cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17534-e17534
Author(s):  
Shine-Gwo Shiah ◽  
Sung-Tau Chou ◽  
Ching-Chuan Kuo ◽  
Ya-Hui Chi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Neck Squamous Cell Carcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples

e17534 Background: Polycomb group (PcG) proteins influence the development and progression of cancer. However, the mechanism that contributes to tumorigenesis have not been fully understood in head and neck squamous cell carcinoma (HNSCC). Methods: The expression of chromobox 8 (CBX8), a member of the polycomb group (PcG) of proteins, on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-410-3p and CBX8 were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Results: Here we found that CBX8 is upregulated in HNSCC tissues and cell lines. Using CBX8 knockdown cDNA microarray, we identify a CBX8-mediated target gene MIPOL1 which is inversely correlated with CBX8 expression in HNSCC tissues. Ectopic expression of MIPOL1 could inhibit tumor invasion and migration, whereas MIPOL1 silencing suppressed these effects in CBX8-knockdown HNSCC cells. Otherwise, depletion of CBX8 also induced p53 activity and increased the expression level of p21 and p27 through MIPOL1-independent manner, which result in cell cycle arrest in G2M phase. Silencing of p53 could inhibit p21 and p27 accumulation in CBX8 knockdown cells. Furthermore, we demonstrated that down-regulation of miR-410-3p promoted HNSCC cells migration and invasion through directly targeting CBX8. Overexpression of miR-410-3p decreased CBX8 expression and reduced migration and invasion, while ectopic expression of CBX8 rescued the miR-410-3p-reduced migration and invasion. In clinical samples, miR-410-3p level closely inversely correlated with CBX8 and positively correlated with MIPOL1. Conclusions: Collectively, our findings indicate that miR-410-3p may act as a tumor suppressor via negatively regulating CBX8. The newly identified miR-410-3p/CBX8/MIPOL1 and miR-410-3p/CBX8/p53 signaling axes may suggest new therapeutic strategies against HNSCC.

Sign in / Sign up

Export Citation Format

Share Document