Dataset Information

Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus.

ABSTRACT: Human papillomavirus (HPV)-positive cases of squamous cell carcinoma of the head and neck (SCCHN) have a much better disease outcome compared to SCCHN cases lacking HPV. Differences in microRNA (miRNA) expression may affect their clinical outcomes.The miRNA expression was studied using microarrays and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in HPV-16-positive and HPV-negative SCCHN cell lines. The role of HPV-16 E6 and E7 oncogenes in altering miRNA expression was investigated using human foreskin keratinocytes (HFKs).The miRNAs miR-363, miR-33, and miR-497 were upregulated, whereas miR-155, miR-181a, miR-181b, miR-29a, miR-218, miR-222, miR-221, and miR-142-5p were downregulated in HPV-positive cells compared to both HPV-negative SCCHN and normal oral keratinocytes. HPV-16 E6 oncogene altered miRNA expression in HFKs and in an HPV-16-positive cell line with E6 knockdown using siRNA.miRNAs differentially expressed in the presence of HPV-16 may provide biomarkers for SCCHN and identify cellular pathways targeted by this virus.

SUBMITTER: Wald AI

PROVIDER: S-EPMC3080748 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus.

Wald Abigail I AI Hoskins Elizabeth E EE Wells Susanne I SI Ferris Robert L RL Khan Saleem A SA

Head & neck 20110401 4

<h4>Background</h4>Human papillomavirus (HPV)-positive cases of squamous cell carcinoma of the head and neck (SCCHN) have a much better disease outcome compared to SCCHN cases lacking HPV. Differences in microRNA (miRNA) expression may affect their clinical outcomes.<h4>Methods</h4>The miRNA expression was studied using microarrays and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in HPV-16-positive and HPV-negative SCCHN cell lines. The role of HPV-16 E6 and E7 oncogenes ...[more]

PMID: 20652977

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Project description:Background:Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods:Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1?, TNF-?, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey's honest significance test (?=0.05). Results:Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions:These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

Project description:A major objective in the management of human papillomavirus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) is to reduce long-term functional ramifications while maintaining oncological outcomes. This study examined the metabolic profile of HPV-positive SCCHN and the potential role of anti-metabolic therapeutics to achieve radiosensitisation as a potential means to de-escalate radiation therapy. Three established HPV-positive SCCHN cell lines were studied (UM-SCC-104, UPCI:SCC154, and VU-SCC-147), together with a typical TP53 mutant HPV-negative SCCHN cell line (UM-SCC-81B) for comparison. Metabolic profiling was performed using extracellular flux analysis during specifically designed mitochondrial and glycolytic stress tests. Sensitivity to ionising radiation (IR) was evaluated using clonogenic assays following no treatment, or treatment with: 25 mM 2-deoxy-D-glucose (glycolytic inhibitor) alone; 20 mM metformin (electron transport chain inhibitor) alone; or 25 mM 2-deoxy-D-glucose and 20 mM metformin combined. Expression levels of p53 and reporters of p53 function (MDM2, p53, Phospho-p53 [Ser15], TIGAR and p21 [CDKN1A]) were examined by western blotting. HPV-positive SCCHN cell lines exhibited a diverse metabolic phenotype, displaying robust mitochondrial and glycolytic reserve capacities. This metabolic profile, in turn, correlated with IR response following administration of anti-metabolic agents, in that both 2-deoxy-D-glucose and metformin were required to significantly potentiate the effects of IR in these cell lines. In contrast to our recently published data on HPV-negative SCCHN cells, which display relative glycolytic dependence, HPV-positive SCCHN cells can only be sensitised to IR using a complex anti-metabolic approach targeting both mitochondrial respiration and glycolysis, reflecting their metabolically diverse phenotype. Notionally, this may provide an attractive platform for treatment de-intensification in the clinical setting by facilitating IR dose reduction to minimise the impact of treatment on long-term function.

Dataset Information

Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus.

Publications

Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus.

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