Project description:Previous studies indicated TCAB1, also known as WRAP53, had oncogenic feature in a certain extend. However, there is none direct study on the function of TCAB1 in tumorigenesis and development of head and neck cancers. First of all, we verified the function of TCAB1 in head and neck cancers. Knockdown TCAB1 would inhibit cell proliferation in Vitro as well as in Vivo, meanwhile, depletion TCAB1 would decrease the invasion potential of OSCC Cal-27 cells. cDNA microarray analysis showed many pathways and factors associated with occurrence and development of carcinomas were implicated in this process. Our study indicated TCAB1 might be a potential target for prognosis and therapy in head and neck cancers.
Project description:Previous studies indicated TCAB1, also known as WRAP53, had oncogenic feature in a certain extend. However, there is none direct study on the function of TCAB1 in tumorigenesis and development of head and neck cancers. First of all, we verified the function of TCAB1 in head and neck cancers. Knockdown TCAB1 would inhibit cell proliferation in Vitro as well as in Vivo, meanwhile, depletion TCAB1 would decrease the invasion potential of OSCC Cal-27 cells. cDNA microarray analysis showed many pathways and factors associated with occurrence and development of carcinomas were implicated in this process. Our study indicated TCAB1 might be a potential target for prognosis and therapy in head and neck cancers. Immunohistochemistry assay and western blot showed TCAB1 was overexpressed in clinical nasopharyngeal carcinoma and head and neck cell lines. Depletion endogenous TCAB1 by shRNA lentivirus in Cal-27 would verify the function of TCAB1 in cells proliferation and invasion. Furthermore, cDNA microarray was performed to detect some pathways or factors involved in the process.
Project description:The critical role of Bmi1 in promoting stem cell properties has been shown in different type of human cancers. Here, we established four stable clones to study Bmi-regulated miRNA expression patterns in head and neck caners.
Project description:The critical role of Bmi1 in promoting stem cell properties has been shown in different type of human cancers. Here, we established four stable clones to study Bmi-regulated miRNA expression patterns in head and neck caners. Bmi1-overexpressing cell lines (FaDu- Bmi1vs. FaDu-pcDNA3 cell line), and knock-down of Bmi1 cell lines (OECM1-sh-Bmi vs. OECM1-sh-Bmi1 cell lines) were established and used for analyzing miRNA expression patterms in Bmi-regulatory mechanism.
Project description:Purpose: Cancer-associated fibroblasts (CAF) have been implicated as potential mediators of checkpoint immunotherapy response. However, the extensive heterogeneity of these cells has precluded rigorous understanding of their immunoregulatory role in the tumor microenvironment Experimental Design: We performed high dimensional single-cell RNA sequencing (scRNA-Seq) on four patient tumors pre- and post-treatment from a neoadjuvant trial of advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the aPD-1 therapy, nivolumab. The head and neck CAF (HNCAF) protein activity profiles, derived from this cohort of paired scRNA-Seq, were used to perform protein activity enrichment analysis on the 28-patient parental cohort of clinically annotated bulk transcriptomic profiles. Ex vivo coculture assays were used to test functional relevance of HNCAF subtypes Results: Fourteen distinct cell types were identified with the fibroblast population showing significant changes in abundance following nivolumab treatment. Among the fibroblast subtypes, HNCAF-0/3 emerged as predictive of nivolumab response, while HNCAF-1 was associated with immunosuppression. Functionally, HNCAF-0/3 were found to reduce TGFβ-dependent PD-1+TIM-3+ exhaustion of CD8 T cells, increase CD103+NKG2A+ resident memory phenotypes, and enhance the overall cytolytic profile of T cells Conclusions: Our findings demonstrate the functional importance of distinct HNCAF subsets in modulating the immunoregulatory milieu of human HNSCC. Additionally, we have identified clinically actionable HNCAF subtypes that can be used as a biomarker of response and resistance in future clinical trials
Project description:Genome wide high resolution assay of copy number in a series of frozen, microdissected head and neck cancers originating from the oral cavity. The objective was to characterize areas of amplification and deletion in head and neck cancers arising from the oral cavity subsite.