Abstract 487: MicroRNA regulation of oral squamous cell carcinoma

Abstract

Abstract Oral squamous cell carcinoma (OSCC) remains the sixth most common human cancer with high mortality rate worldwide. Understanding the molecular mechanisms is important for development of an effective treatment for the disease. MicroRNA is a short, noncoded nucleotide playing an important role in tumorigenesis and metastasis. This study is to identify novel microRNAs and their targets in order to understand the molecular mechanisms underlying OSCC and metastasis using label-free proteomics and microRNA microarray techniques. Human oral tissue biopsies from three groups of subjects who had benign, localized carcinoma and distal carcinoma were collected from the archived tissue bank at Pathology in Creighton University. Total RNA and proteins were extracted from the core biopsy of the same subject. MicroRNA identification was performed by using Affymetrix GeneChip miRNA arrays and comprehensive data analysis. Protein was analyzed by using label-free LTQ orbit trap mass spectrometry. Forty-four miRNAs were upregulated significantly, including let-7b, miR-720, miR-21, and miR-1274b, while 41 miRNAs were remarkably downregulated, including miR-195, and miR-932, at localized and distal carcinoma compared to benign tissues. Additionally, as compared to benign, 38 miRNAs upregulated at local carcinoma were downregulated significantly at distal carcinoma, while other 17 miRNAs downregulated significantly at localized carcinoma were upregulated gigantically at distal carcinoma. Those miRNAs were further validated by qRT-PCR and FISH. Among those upregulated at both local and distal, miR-720 was further studied, and tryptase alpha-1 as its target was identified. MicroRNA-720 mimics suppressed significantly the expression of tryptase alpha-1 in cultured human OSCC stem cell lines. Results from miR-720 tissue microarray analysis showed that 98.8% of sensitivity and 100% of specificity for OSCC detection were achieved, suggesting that miR-720 may be developed as a novel biomarker for detection of human OSCC. Citation Format: Gary Guishan Xiao, Min Cao. MicroRNA regulation of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 487.