Abstract 4323: 1,25-Dihydroxyvitamin D3 inhibits oral squamous cell carcinoma cell growth via microRNA regulation

Abstract

Abstract Objective: Oral squamous cell carcinomas (OSCC) is one of top ten cancers lead to death in USA. This study focused on the impacts of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on the inhibition of OSCC growth in vitro and the alteration of microRNA (miRNA) expression profile by the treatment. Materials and Methods: 1,25(OH)2D3-associated apoptosis, cell cycle arrest, and proliferative effect in cultured OSCC cells were assessed using flow cytometry and western blotting methods. miRNA expression profiles were measured using nanoString Sprint Profiller and the Nanostring human miRNA panel. More miRNAs functional pathways were retrieved through bioinformatics using Qiagen IPA system. Results: 1,25(OH)2D3 was found to inhibit the growth of human JHU-22 OSCC cells in a dose-dependent manner with IC50 of 1.56 x 10-6 M. High levels of apoptotic cells and related biomarkers were obtained when the cells were treated with 1,25(OH)2D3. Over 20 miRNAs were upregulated and 23 downregulated by more than two folds, in 1,25(OH)2D3 treated versus untreated JHU-22 cells. Bioinformatics analysis showed molecular functions of most dysregulated miRNAs. For example, MiR-125b-5p upregulated caspases number 2, 6, 7 in addition to upregulating apoptosis facilitator like BCL-2, BIM, and AIF. Conclusion: Our data suggested that 1,25(OH)2D3 function as a OSCC inhibiter is through regulating miRNA expression profile and miRNA function directly or indirectly. 1,25(OH)2D3 has potential to be an anticancer agent for OSCC prevention and treatment. Fold change of top ten unregulated and down regulated miRNAs at nine hour treatment.miRNAControl (C9)Vitamin D (D9)C9/D9hsa-miR-624-3p8283.5hsa-miR-52110272.7hsa-miR-221-5p11292.64hsa-miR-1301-3p7182.57hsa-miR-520a-3p8202.5hsa-miR-153-3p12282.33hsa-miR-122-5p16372.31hsa-miR-120615342.27hsa-miR-125b-5p68615472.26hsa-miR-450b-3p492.25hsa-miR-613219-2.33hsa-miR-147b2611-2.36hsa-miR-525-3p125-2.40hsa-miR-5196-3p+hsa-miR-6732-3p187-2.57hsa-miR-181b-5p+hsa-miR-181d-5p218-2.63hsa-miR-182-3p3212-2.67hsa-miR-941228-2.75hsa-miR-671-3p176-2.83hsa-miR-944186-3.00hsa-miR-1245b-3p246-4.00 Citation Format: Heba Said Ismail Hussein, Wei Wang, Liang Shan, Karl Thompson, Kareem Washington, Gihane Madkour, Xinbin Gu. 1,25-Dihydroxyvitamin D3 inhibits oral squamous cell carcinoma cell growth via microRNA regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4323.