MEIS1‑regulated miR‑488‑3p suppresses the malignant progression of laryngeal squamous cell carcinoma by targeting ACVR1C.

MEIS1 调控的 miR-488-3p 通过靶向 ACVR1C 抑制喉鳞状细胞癌的恶性进展

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作者:Zhang Chunming, Hao Wenjing, Wang Xinfang, Guo Huina, He Long, Yang Jiao, Wang Ying, Zheng Xiwang, Li Zhongxun, Han Qi, Wen Liqi, Liu Hongliang
Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor originating from the mucosal epithelium of the larynx. MicroRNA (miR)‑488‑3p has non‑negligible multifaceted roles in some types of cancer; however, its association with LSCC has not yet been reported. Our prior RNA sequencing data indicated that miR‑488‑3p expression is downregulated in LSCC tissue, yet the detailed function and regulatory mechanism of miR‑488‑3p in LSCC remain unknown. In the present study, quantitative PCR analysis corroborated the significant downregulation of miR‑488‑3p in LSCC tumor tissues, with this downregulation being strongly associated with malignant progression in LSCC. Furthermore, overexpression of miR‑488‑3p suppressed LSCC cell proliferation, colony formation, migration, invasion, xenograft tumor growth and epithelial‑mesenchymal transition. Mechanistically, miR‑488‑3p directly interacted with the 3' untranslated region of activin A receptor type 1C (ACVR1C) and downregulated ACVR1C expression. Functional experiments revealed that miR‑488‑3p suppressed the malignant phenotypes of LSCC via ACVR1C. Additionally, bioinformatics analysis coupled with chromatin immunoprecipitation assay revealed that myeloid ecotropic viral integration site 1 (MEIS1) promoted the expression of miR‑488‑3p transcriptionally by directly binding its promoter region. Collectively, the results demonstrated that miR‑488‑3p acts as a tumor suppressor molecule in LSCC, and a role was established for the MEIS1/miR‑488‑3p/ACVR1C axis in regulating LSCC progression, thus providing novel potential biomarkers and targets for patients with LSCC.

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