Int J Biol Sci 2021; 17(15):4327-4339. doi:10.7150/ijbs.64851 This issue

Research Paper

miR-34a-5p functions as a tumor suppressor in head and neck squamous cell cancer progression by targeting Flotillin-2

Xiang Li1,2,3, Shouwei Zhao1, Yu Fu1,2, Ping Zhang1,2, Zhenxing Zhang1,2, Jie Cheng1,2, Laikui Liu1,2, Hongbing Jiang1,2,3✉

1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.
2. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.
3. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine.

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Citation:
Li X, Zhao S, Fu Y, Zhang P, Zhang Z, Cheng J, Liu L, Jiang H. miR-34a-5p functions as a tumor suppressor in head and neck squamous cell cancer progression by targeting Flotillin-2. Int J Biol Sci 2021; 17(15):4327-4339. doi:10.7150/ijbs.64851. Available from https://www.ijbs.com/v17p4327.htm

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Abstract

Graphic abstract

While a number of therapeutic advances have been made in recent years, the overall survival of patients with head and neck squamous cell cancer (HNSCC) remains poor. MicroRNAs (miRNAs) are key drivers of oncogenic progression, with miR-34a-5p downregulation having been observed in many different tumor types. Here, we assessed the link between miR-34a-5p and HNSCC progression and the mechanistic basis for this relationship. Levels of miR-34a-5p in HNSCC tumors and cell lines were assessed via qPCR, after which we explored the functional importance of this miRNA in this oncogenic setting. Through luciferase reporter assays, the ability of miR-34a-5p to regulate flotillin-2 (FLOT-2) was further clarified. Overall, these analyses revealed that HNSCC tumors and cells exhibited marked miR-34a-5p downregulation that was linked to the progression of this tumor type. At a functional level, miR-34a-5p constrained the proliferation, migratory/invasive activity, and epithelial-mesenchymal transition induction in HNSCC cells. At the mechanistic level, miR-34a-5p was found to suppress FLOT-2 expression and to activate the MEK/ERK1/2 pathway. Overall, these results suggest that miR-34a-5p can function as a tumor suppressor miRNA in HNSCC owing to its ability to target FLOT-2, highlighting the promise of targeting this regulatory axis to treat HNSCC.

Keywords: Head and Neck Squamous Cell Carcinoma, miR-34a-5p, FLOT-2, MEK/ERK1/2