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miR-34a-5p functions as a tumor suppressor in head and neck squamous cell cancer progression by targeting Flotillin-2.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2021 Oct 21; Vol. 17 (15), pp. 4327-4339. Date of Electronic Publication: 2021 Oct 21 (Print Publication: 2021). - Publication Year :
- 2021
-
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.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Down-Regulation
Epithelial-Mesenchymal Transition physiology
Extracellular Signal-Regulated MAP Kinases genetics
Extracellular Signal-Regulated MAP Kinases metabolism
Female
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms genetics
Humans
MAP Kinase Kinase Kinases genetics
MAP Kinase Kinase Kinases metabolism
MAP Kinase Signaling System
Male
Membrane Proteins genetics
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs antagonists & inhibitors
MicroRNAs genetics
Middle Aged
Molecular Mimicry
Neoplasms, Experimental
Squamous Cell Carcinoma of Head and Neck genetics
Head and Neck Neoplasms metabolism
Membrane Proteins metabolism
MicroRNAs metabolism
Squamous Cell Carcinoma of Head and Neck metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 17
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34803501
- Full Text :
- https://doi.org/10.7150/ijbs.64851