PMID- 37081981 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231201 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 13 DP - 2023 TI - Investigating miR-9 as a mediator in laryngeal cancer health disparities. PG - 1096882 LID - 10.3389/fonc.2023.1096882 [doi] LID - 1096882 AB - BACKGROUND: For 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. METHODS: Bioinformatic 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. RESULTS: Northern 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. CONCLUSION: Collectively, 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. CI - Copyright (c) 2023 Gobin, Inkabi, Lattimore, Gu, Menefee, Rodriguez, Kates, Fields, Bian, Silver, Xing, Yates, Renne, Xie and Fredenburg. FAU - Gobin, Christina AU - Gobin C AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. FAU - Inkabi, Samuel AU - Inkabi S AD - College of Graduate Health Studies, A.T. Still University, Kirksville, MO, United States. FAU - Lattimore, Chayil C AU - Lattimore CC AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. FAU - Gu, Tongjun AU - Gu T AD - Interdisciplinary Center for Biotechnology Research Bioinformatics Core Facility, University of Florida, Gainesville, FL, United States. FAU - Menefee, James N AU - Menefee JN AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. FAU - Rodriguez, Mayrangela AU - Rodriguez M AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. FAU - Kates, Heather AU - Kates H AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. FAU - Fields, Christopher AU - Fields C AD - Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States. FAU - Bian, Tengfei AU - Bian T AD - Department of Medicinal Chemistry, University of Florida, Gainesville, FL, United States. FAU - Silver, Natalie AU - Silver N AD - Head and Neck Institute/Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States. FAU - Xing, Chengguo AU - Xing C AD - Department of Medicinal Chemistry, University of Florida, Gainesville, FL, United States. FAU - Yates, Clayton AU - Yates C AD - Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, United States. AD - Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States. AD - Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, United States. FAU - Renne, Rolf AU - Renne R AD - Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, United States. FAU - Xie, Mingyi AU - Xie M AD - Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States. FAU - Fredenburg, Kristianna M AU - Fredenburg KM AD - Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States. LA - eng GR - K08 DE029503/DE/NIDCR NIH HHS/United States GR - P01 CA214091/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20230404 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC10112398 OTO - NOTNLM OT - ABCC1 OT - MAP1B OT - cancer health disparities OT - head and neck cancer OT - laryngeal squamous cell carcinoma OT - miR-9 COIS- During the writing of this report, CY received personal fees from Riptide Biosciences, QED Therapeutics, and Amgen, and other income from Riptide Biosciences outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/04/21 06:41 MHDA- 2023/04/21 06:42 PMCR- 2023/01/01 CRDT- 2023/04/21 02:16 PHST- 2022/11/12 00:00 [received] PHST- 2023/03/06 00:00 [accepted] PHST- 2023/04/21 06:42 [medline] PHST- 2023/04/21 06:41 [pubmed] PHST- 2023/04/21 02:16 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2023.1096882 [doi] PST - epublish SO - Front Oncol. 2023 Apr 4;13:1096882. doi: 10.3389/fonc.2023.1096882. eCollection 2023.