Investigating miR-9 as a mediator in laryngeal cancer health disparities

Frontiers in Oncology

Oncology

Samuel Inkabi¹  Christopher Fields²  Mingyi Xie³  Chengguo Xing⁴  Tengfei Bian⁴  Rolf Renne⁵  Kristianna M. Fredenburg⁶  Mayrangela Rodriguez⁶  Heather Kates⁶  Chayil C. Lattimore⁶  James N. Menefee⁶  Christina Gobin⁶  Clayton Yates⁷  Natalie Silver⁸  Tongjun Gu⁹ 

[1] College of Graduate Health Studies, A.T. Still University, Kirksville, MO, United States;Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States;Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States;Department of Medicinal Chemistry, University of Florida, Gainesville, FL, United States;Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, United States;Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States;Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, United States;Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Head and Neck Institute/Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States;Interdisciplinary Center for Biotechnology Research Bioinformatics Core Facility, University of Florida, Gainesville, FL, United States;

关键词: cancer health disparities;    laryngeal squamous cell carcinoma;    miR-9;    head and neck cancer;    ABCC1;    MAP1B;   

DOI  :  10.3389/fonc.2023.1096882

 received in 2022-11-12, accepted in 2023-03-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundFor several decades, Black patients have carried a higher burden of laryngeal cancer among all races. Even when accounting for sociodemographics, a disparity remains. Differentially expressed microRNAs have been linked to racially disparate clinical outcomes in breast and prostate cancers, yet an association in laryngeal cancer has not been addressed. In this study, we present our computational analysis of differentially expressed miRNAs in Black compared with White laryngeal cancer and further validate microRNA-9-5p (miR-9-5p) as a potential mediator of cancer phenotype and chemoresistance.MethodsBioinformatic analysis of 111 (92 Whites, 19 Black) laryngeal squamous cell carcinoma (LSCC) specimens from the TCGA revealed miRNAs were significantly differentially expressed in Black compared with White LSCC. We focused on miR-9-5 p which had a significant 4-fold lower expression in Black compared with White LSCC (p<0.05). After transient transfection with either miR-9 mimic or inhibitor in cell lines derived from Black (UM-SCC-12) or White LSCC patients (UM-SCC-10A), cellular migration and cell proliferation was assessed. Alterations in cisplatin sensitivity was evaluated in transient transfected cells via IC50 analysis. qPCR was performed on transfected cells to evaluate miR-9 targets and chemoresistance predictors, ABCC1 and MAP1B.ResultsNorthern blot analysis revealed mature miR-9-5p was inherently lower in cell line UM-SCC-12 compared with UM-SCC-10A. UM -SCC-12 had baseline increase in cellular migration (p < 0.01), proliferation (p < 0.0001) and chemosensitivity (p < 0.01) compared to UM-SCC-10A. Increasing miR-9 in UM-SCC-12 cells resulted in decreased cellular migration (p < 0.05), decreased proliferation (p < 0.0001) and increased sensitivity to cisplatin (p < 0.001). Reducing miR-9 in UM-SCC-10A cells resulted in increased cellular migration (p < 0.05), increased proliferation (p < 0.05) and decreased sensitivity to cisplatin (p < 0.01). A significant inverse relationship in ABCC1 and MAP1B gene expression was observed when miR-9 levels were transiently elevated or reduced in either UM-SCC-12 or UM-SCC-10A cell lines, respectively, suggesting modulation by miR-9.ConclusionCollectively, these studies introduce differential miRNA expression in LSCC cancer health disparities and propose a role for low miR-9-5p as a mediator in LSCC tumorigenesis and chemoresistance.

【 授权许可】

Unknown   
Copyright © 2023 Gobin, Inkabi, Lattimore, Gu, Menefee, Rodriguez, Kates, Fields, Bian, Silver, Xing, Yates, Renne, Xie and Fredenburg