Liu Han, Zheng Jun, Ren Zuodong, Shen Kangyuan, Zeng Yan
Precision Clinical Laboratory, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, 524037, Guangdong, China.
Department of Stomatology, Central People's Hospital of Zhanjiang, Zhanjiang, 524037, Guangdong, China.
J Transl Med. 2025 Aug 7;23(1):881. doi: 10.1186/s12967-025-06910-8.
Oral squamous cell carcinoma (OSCC) is marked by aggressive metastasis and poor prognosis, with epithelial-mesenchymal transition (EMT) serving as a pivotal process in tumor metastasis. Consequently, identifying critical targets and elucidating the underlying mechanisms that drive OSCC metastasis are vital for enhancing patient prognosis. This study sought to clarify the significance and underlying molecular mechanisms of the miR-107/synuclein gamma (SNCG) axis in the regulation of OSCC migration, invasion, and EMT progression.
Peripheral blood from 26 OSCC patients and 24 controls assessed miR-107 expression, with GEO analysis for clinical significance. The effects of miR-107 and SNCG on OSCC migration, invasion and EMT in vivo and in vitro were assessed via wound healing, Transwell assays, qRT-PCR, WB and xenograft model.
miR-107 was downregulated, while SNCG was upregulated in OSCC tissues. miR-107 served as a direct regulator of SNCG, leading to its downregulation. Gain- and loss-of-function studies demonstrated that SNCG promoted OSCC cell migration, invasion and EMT progression, while miR-107 inhibited EMT and exerted the opposite effect. These findings were confirmed in a nude mouse model, where miR-107 counteracted SNCG-induced tumor growth and EMT progression. Mechanistically, SNCG increased ERK1/2 and NF-κB p65 phosphorylation without altering total protein levels, while miR-107 mimic partially reversed these effects, suggesting that the miR-107/SNCG axis regulates migration, invasion and EMT progression through the ERK1/2 and NF-κB pathways.
Overall, our findings elucidated that miR-107 attenuated migration and EMT in OSCC by targeting SNCG and inhibiting the ERK1/2/NF-κB pathway, providing novel potential therapeutic targets for OSCC.
口腔鳞状细胞癌（OSCC）具有侵袭性转移和预后不良的特点，上皮-间质转化（EMT）是肿瘤转移的关键过程。因此，确定关键靶点并阐明驱动OSCC转移的潜在机制对于改善患者预后至关重要。本研究旨在阐明miR-107/γ-突触核蛋白（SNCG）轴在调节OSCC迁移、侵袭和EMT进展中的意义及潜在分子机制。
对26例OSCC患者和24例对照者的外周血进行检测以评估miR-107表达，并通过GEO分析其临床意义。通过伤口愈合实验、Transwell实验、qRT-PCR、WB和异种移植模型评估miR-107和SNCG对OSCC体内和体外迁移、侵袭及EMT的影响。
OSCC组织中miR-107表达下调，而SNCG表达上调。miR-107是SNCG的直接调节因子，可导致其表达下调。功能获得和缺失研究表明，SNCG促进OSCC细胞迁移、侵袭和EMT进展，而miR-107抑制EMT，发挥相反作用。在裸鼠模型中证实了这些发现，其中miR-107可抵消SNCG诱导的肿瘤生长和EMT进展。机制上，SNCG增加ERK1/2和NF-κB p65的磷酸化水平，但不改变总蛋白水平，而miR-107模拟物可部分逆转这些作用，表明miR-107/SNCG轴通过ERK1/2和NF-κB途径调节迁移、侵袭和EMT进展。
总体而言，我们的研究结果表明，miR-107通过靶向SNCG并抑制ERK1/2/NF-κB途径减弱OSCC的迁移和EMT，为OSCC提供了新的潜在治疗靶点。
