MicroRNA-22 targets FMNL2 to inhibit melanoma progression via the regulation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition

L. Shi, J.-W. Huo, S.-S. Chen, J.-X. Xue, W.-Y. Gao, X.-Y. Li, Y.-H. Song, H.-T. Xu, X.-W. Zhu, K. Chen

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China. huuuuo8@126.com

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• Oncology

OBJECTIVE: Melanoma is regarded as one common malignancy in skin cancers, and there is growing evidence that microRNAs (miRNAs) play a vital role in the oncogenesis of tumors. This study aimed to investigate the roles and mechanism of miR-22 in melanoma.
PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect the expressions of miR-22 and mRNA. The functions of miR-22 in melanoma cell proliferation, migration and invasion were investigated with functional assays, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay. Western blots were utilized to examine the protein expressions. Luciferase reporter analysis was conducted to confirm the interactions between formin-like 2 (FMNL2) and miR-22 in melanoma cells. FMNL2 expression levels in melanoma tissues were investigated by immunohistochemistry (IHC) assays.
RESULTS: The qRT-PCR analysis demonstrated significant decreased miR-22 expressions in melanoma tissues. Decreased miR-22 in melanoma tissues were correlated with adverse clinicopathologic features and poor prognosis. Functional assays indicated that upregulation inhibited melanoma cell proliferation, invasion and migration capacities. Luciferase reporter assays showed that FMNL2 was targeted by miR-22 in melanoma cells. Western blots indicated that miR-22 exerted anti-tumor functions by regulating the Wnt/β-catenin and epithelial-mesenchymal transition (EMT).
CONCLUSIONS: Our findings showed that miR-22 served as a tumor suppressor in melanoma progression, implying that miR-22 may function as a novel therapeutic target and prognostic biomarker for melanoma treatments.

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