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MFAP2 通过自噬激活 Wnt/β-catenin 信号通路促进口腔鳞状细胞癌的进展。

MFAP2 promotes the progression of oral squamous cell carcinoma by activating the Wnt/β-catenin signaling pathway through autophagy.

机构信息

Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China.

School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2023 Aug 17;55(9):1445-1455. doi: 10.3724/abbs.2023079.

DOI:10.3724/abbs.2023079
PMID:37592847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10520470/
Abstract

Microfibrillar-associated protein 2 (MFAP2) is a small glycoprotein that is involved in vascular development and metabolic disease. The present study aims to explore the regulatory role of MFAP2 in the development and progression of oral squamous cell carcinoma (OSCC), including the underlying mechanisms. MFAP2 expression and its association with the progression of OSCC are explored using bioinformatics. MFAP2 expression in OSCC tissues is detected by immunohistochemical staining. SCC15 cell migration, invasion, apoptosis, proliferation, and viability are detected by wound healing, Transwell, flow cytometry, colony formation, and cell counting kit-8 assays. An experiment is used to detect tumor formation. Western blot analysis is used to determine MFAP2's regulatory role in autophagy and the Wnt/β-catenin signaling pathway. MFAP2 is highly expressed in SCC15 cells and OSCC tissues, which correlates positively with the poor prognosis of patients with OSCCs. Functionally, MFAP2 promotes oncogenic autophagy to increase cell invasion, migration, and proliferation but inhibits apoptosis in SCC15 cells and promotes tumor growth . Mechanistically, MFAP2 upregulates autophagy and Wnt/β-catenin signaling to stimulate OSCC development. Intriguingly, regulation of Wnt/β-catenin signaling dependent on autophagy contributes to the malignant behaviors of SCC15 cells. MFAP2 could serve as a novel biomarker for OSCC and could affect OSCC tumorigenesis and development via autophagic regulation of Wnt/β-catenin signaling.

摘要

微纤维相关蛋白 2(MFAP2)是一种参与血管发育和代谢疾病的小糖蛋白。本研究旨在探讨 MFAP2 在口腔鳞状细胞癌(OSCC)发展和进展中的调节作用,包括潜在机制。使用生物信息学方法探讨 MFAP2 表达及其与 OSCC 进展的相关性。通过免疫组织化学染色检测 OSCC 组织中 MFAP2 的表达。通过划痕愈合、Transwell、流式细胞术、集落形成和细胞计数试剂盒-8 测定检测 SCC15 细胞迁移、侵袭、凋亡、增殖和活力。进行实验检测肿瘤形成。Western blot 分析用于确定 MFAP2 在自噬和 Wnt/β-catenin 信号通路中的调节作用。MFAP2 在 SCC15 细胞和 OSCC 组织中高表达,与 OSCC 患者的不良预后呈正相关。功能上,MFAP2 促进致癌自噬,增加细胞侵袭、迁移和增殖,但抑制 SCC15 细胞凋亡,并促进肿瘤生长。机制上,MFAP2 上调自噬和 Wnt/β-catenin 信号通路,刺激 OSCC 发展。有趣的是,自噬依赖性 Wnt/β-catenin 信号通路的调节有助于 SCC15 细胞的恶性行为。MFAP2 可以作为 OSCC 的新型生物标志物,并通过自噬调节 Wnt/β-catenin 信号通路影响 OSCC 肿瘤发生和发展。

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