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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。

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

作者信息

Zhang Chunming, Hao Wenjing, Wang Xinfang, Guo Huina, He Long, Yang Jiao, Wang Ying, Zheng Xiwang, Li Zhongxun, Han Qi, Wen Liqi, Liu Hongliang

机构信息

Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Department of Anatomy, The Basic Medical School of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

出版信息

Int J Mol Med. 2025 Sep;56(3). doi: 10.3892/ijmm.2025.5583. Epub 2025 Jul 19.

Abstract

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.

摘要

喉鳞状细胞癌(LSCC)是一种起源于喉黏膜上皮的常见恶性肿瘤。微小RNA(miR)-488-3p在某些类型的癌症中具有不可忽视的多方面作用;然而,其与LSCC的关联尚未见报道。我们之前的RNA测序数据表明,miR-488-3p在LSCC组织中的表达下调,但其在LSCC中的详细功能和调控机制仍不清楚。在本研究中,定量PCR分析证实了miR-488-3p在LSCC肿瘤组织中显著下调,且这种下调与LSCC的恶性进展密切相关。此外,miR-488-3p的过表达抑制了LSCC细胞的增殖、集落形成、迁移、侵袭、异种移植肿瘤生长以及上皮-间质转化。机制上,miR-488-3p直接与激活素A受体1C(ACVR1C)的3'非翻译区相互作用,并下调ACVR1C的表达。功能实验表明,miR-488-3p通过ACVR1C抑制LSCC的恶性表型。此外,生物信息学分析结合染色质免疫沉淀试验表明,髓系嗜亲性病毒整合位点1(MEIS1)通过直接结合其启动子区域转录促进miR-488-3p的表达。总体而言,结果表明miR-488-3p在LSCC中作为一种肿瘤抑制分子发挥作用,并确立了MEIS1/miR-488-3p/ACVR1C轴在调节LSCC进展中的作用,从而为LSCC患者提供了新的潜在生物标志物和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/868e/12270386/a560c1a7aa1e/ijmm-56-03-05583-g00.jpg

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