Circular RNA FAT1 (hsa_circ_0001461) Promotes the Progression of Oral Squamous Cell Carcinoma by Regulating miR-181d-5p/miR-199a-5p

Jijun Chen; Liang Wang; Danhua Ma; Hongyan Gao; Yuyuan Shi

Authors

Jijun Chen Department of Stomatology, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, 315000 Ningbo, Zhejiang, China Author
Liang Wang Department of Stomatology, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, 315000 Ningbo, Zhejiang, China Author
Danhua Ma Zhejiang Provincial Key Laboratory of Diagnosis, Treatment and Research of Digestive System Tumors, 315000 Ningbo, Zhejiang, China Author
Hongyan Gao Zhejiang Provincial Key Laboratory of Diagnosis, Treatment and Research of Digestive System Tumors, 315000 Ningbo, Zhejiang, China Author
Yuyuan Shi Department of Stomatology, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, 315000 Ningbo, Zhejiang, China Author

Keywords:

Oral squamous cell carcinoma, hsa_circ_0001461, MiR-181d-5p, MiR-199a-5p, Circular RNA

Abstract

Objective: To explore the role and mechanism of circular RNA FAT1 (hsa_circ_0001461)-miR-181d-5p/miR-199a-5p axis in the biological functions of oral squamous cell carcinoma (OSCC) cells. Methods: The clinical tissues of 30 OSCC patients were collected, and the expressions of circFAT1, miR-181d-5p and miR-199a-5p in OSCC tissues and cells were detected by real-time quantitative PCR. starBase and dual-luciferase reporter genes were used to verify the targeting relationship between miR-181d-5p/miR-199a-5p and circFAT1. Functional experiments included CCK-8, Transwell, and flow cytometry to determine the effects of circFAT1-miR-181d-5p/miR-199a-5p axis on OSCC cell viability, migration, invasion, apoptosis and cycle. Western blot combined with LY294002 treatment was used to measure the expressions of PI3K/Akt/mTOR signaling pathway-related proteins. Results: The circFAT1 expression was increased, and miR-181d-5p and miR-199a-5p expressions were decreased in OSCC (p < 0.001). CircFAT1 could target miR-181d-5p and miR-199a-5p simultaneously (p < 0.01). CircFAT1 silencing, miR-181d-5p mimic and miR-199a-5p mimic inhibited OSCC cell viability, migration, invasion and cycle progression, induced apoptosis, and suppressed the activation of PI3K/Akt/mTOR pathway, while overexpressed circFAT1, miR-181d-5p inhibitor and miR-199a-5p inhibitor did the opposite (p < 0.05). MiR-181d-5p and miR-199a-5p partially reversed the effect of circFAT1 on the biological functions of OSCC cells (p < 0.05). LY294002 pretreatment offset the role of circFAT1 overexpression in PI3K/Akt/mTOR pathway and cell viability (p < 0.05). Conclusion: CircFAT1 promotes the malignant progression of OSCC cells by regulating miR-181d-5p/miR-199a-5p.

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