Abstract C042: Low miR-9 impacts tumorigenesis and chemoresistance in Black compared with White laryngeal squamous cell carcinoma

Abstract

Abstract Background: Advanced stage laryngeal squamous cell carcinoma (LSCC) has sustained one of the lowest five-year survival rates across all other head and neck squamous cancers. For several decades, Black patients have maintained a greater likelihood of presenting with advanced LSCC and a higher overall mortality rate compared with White patients. Even when accounting for sociodemographics, a disparity remains, underscoring the importance of investigating the biologic basis of this disparity. Differential microRNA (miRNA) expression has been linked to racially disparate clinical outcomes in other cancers including breast and prostate, but remains underdetermined in LSCC. We present our findings where we investigated miR-9 levels and their influence on LSCC tumorigenesis and chemoresistance using in vitro cell lines derived from Black and White patients. Methods: We previously identified miR-9-5p as significantly lower (5X) in Black compared with White advanced stage LSCC in vivo samples. For functional studies, we obtained two LSCC cell lines derived from a Black patient (UM-SCC-12) and from a White patient (UM-SCC-10A) (provided by Tom Carey, University of Michigan). After transfection with either miR-9 mimic or inhibitor, we used the scratch wound assay to assess cell migration and the cell titer blue assay to assess cell proliferation and chemoresistance. Results: Prior to transfection, we found that UM-SCC-12 had baseline increases in cellular migration, proliferation and chemoresistance compared to UM-SCC-10A. By Northern blot analysis, we further determined that mature miR-9-5p was inherently 5X lower in UM-SCC-12 compared with UM-SCC-10A. After transient transfection, we noted that overexpressing miR-9 in UM-SCC-12 resulted in decreased cellular migration, decreased proliferation and increased chemosensitivity compared to a mock oligo control, whereas inhibiting miR-9 in UM-SCC-10A resulted in increased cellular migration, increased proliferation and decreased chemosensitivity compared to a mock oligo control. Conclusion: Collectively, these studies support that low miR-9 may play a role in LSCC tumorigenesis and chemoresistance. In this manner, it may contribute to cancer health disparate outcomes observed in advanced stage LSCC. Future studies will involve characterizing significant downstream mediators of low miR-9-5p gene regulation. Citation Format: Christina Gobin, Samuel Inkabi, Chayil Lattimore, James Menefee, Tengfei Bian, Christopher Fields, Mingyi Xie, Chengguo Xing, Kristianna Fredenburg. Low miR-9 impacts tumorigenesis and chemoresistance in Black compared with White laryngeal squamous cell carcinoma [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C042.