A High-Content Screening Approach to Identify MicroRNAs Against Head and Neck Cancer Cell Survival and EMT in an Inflammatory Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer types. Metastasis, the main cause of death by cancer, can be promoted by an inflammatory microenvironment, which induces epithelial-mesenchymal transition (EMT) through a NF-κB-mediated stabilization of Snail. Here, we aimed to explore how microRNAs (miRs) can affect cell survival and EMT in HNSCC cells under an inflammatory microenvironment. By using a high-content screening (HCS) approach, we evaluated alterations in morphometric parameters, as well as expression/localization of Snail/Slug, in HNSCC cells primed with TNF-α. Based on those quantitation, we established the optimal experimental conditions of EMT induction driven by TNF-α. Those conditions were applied to cells transfected with distinct miRs (N = 31), followed by clusterization of miRs based on alterations related to cell survival and EMT. The signaling pathways enriched with molecular targets from each group of miRs were identified by in silico analyses. Finally, cells were transfected with siRNAs against signaling pathways targeted by miRs with anti-survival/EMT effect and evaluated for alterations in cell survival and EMT. Overall, we observed that TNF-α, at 20 ng/ml, induced EMT-related changes in cell morphology, Snail/Slug expression, and cell migration. Predicted targets of miRs with anti-survival/EMT effect were enriched with targets of NF-κB, PI3K/ATK, and Wnt/beta catenin pathways. Strikingly, i...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

Related Links:

This report is the first study where NGS analysis based on multiplex-PCR is used to demonstrate the imminent occurrence of missense SMAD4 mutations in HNSCC cells. The gene analysis that we performed may support the identification of SMAD4 mutations as a diagnostic marker or even as a potential therapeutic target in head and neck cancer. Moreover, the analytic strategy proposed for the detection of mutations in the SMAD4 gene may be validated as a platform to assist mutation screening.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Guo B, Wang L, Qin X, Shen Y, Ma C Abstract A number of studies have reported the upregulation and functional roles of Jumonji domain-containing protein 6 (JMJD6) in various types of cancer. However, little is known regarding the clinical significance of JMJD6 in head and neck squamous cell carcinoma (HNSCC), particularly in terms of large-cohort data. In the present study, bioinformatics analysis was performed, using the University of California Santa Cruz Xena Browser and the Gene Expression Profiling Interactive Analysis 2 server, based on the Cancer Genome Atlas HNSCC cohort. In addition, a validation ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Abstract Cancer stem cells (CSCs) play a key role in carcinogenesis and progression of head and neck squamous cell carcinomas (HNSCC). The most common markers indicating for CSCs are: CD44, CD24, CD133, ALDH1A1. Our objective was to evaluate the prognostic potential of CSC markers in HNSCC. The study included 49 patients treated for primary HNSCC, 11 patients with upper respiratory tract epithelial dysplasia and 12 subjects with the normal pharyngeal mucosa as a control group. The frequency and expression levels of the four CSC markers were assessed by immunohistochemistry. Univariate and multivariate analyses wer...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Abstract Over the past decades, studies of phytochemicals as modifiers of radiotherapeutic efficacy have become increasingly popular to improve the treatment outcome of human malignancies. In the current comprehensive review article, radiosensitizing effects of curcumin, a yellow-colored polyphenolic constituent of turmeric, in various preclinical cancer models, both In Vitro and In Vivo, are presented. Attenuation of radioadaptation and augmentation of irradiation-induced cancer cell killing are achieved through multifaceted action of curcumin on suppression of prosurvival and antiapoptotic factors. Mos...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
Cancers, Vol. 11, Pages 1583: CD200 Induces Epithelial-to-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma via β-Catenin-Mediated Nuclear Translocation Cancers doi: 10.3390/cancers11101583 Authors: Seung-Phil Shin A-RA Goh Hyeon-Gu Kang Seok-Jun Kim Jong-Kwang Kim Kyung-Tae Kim John H Lee Yong-Soo Bae Yuh-Seog Jung Sang-Jin Lee The membrane glycoprotein CD200 binds to its receptor CD200R1 and induces tolerance, mainly in cells of the myeloid lineage; however, information regarding its role in solid tumors is limited. Here, we investigated whether CD200 expression, which is enri...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In conclusion, we proposed that EZH2 regulates EMT and tumor invasion and metastasis in HNSCC by governing the STAT3/VEGFR2 axis. These findings provide a rationale for developing novel strategies to treat invasive and metastatic HNSCC via targeting the EZH2/STAT3/VEGFR2 pathway. PMID: 31545422 [PubMed - as supplied by publisher]
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Abstract Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In conclusion, ieTILs and strTILs were non-redundant biomarkers in HNSCC and should be evaluated separately. The identified prognostic markers should be evaluated for predictivity in ICB-treated patients.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
In this study, we aimed to determine the potential clini...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
vari Licitra De Cecco Patients (pts) with head and neck squamous cell carcinoma (HNSCC) have different epidemiologic, clinical, and outcome behaviors in relation to human papillomavirus (HPV) infection status, with HPV-positive patients having a 70% reduction in their risk of death. Little is known about the molecular heterogeneity in HPV-related cases. In the present study, we aim to disclose the molecular subtypes with potential biological and clinical relevance. Through a literature review, 11 studies were retrieved with a total of 346 gene-expression data points from HPV-positive HNSCC pts. Meta-analysis and ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Epithelial Cancer | Genetics | Head and Neck Cancer | HNSCC | Skin Cancer | Squamous Cell Carcinoma