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miR-199a-5p 调控的 SMARCA4 促进口腔鳞状细胞癌肿瘤发生。

MiR-199a-5p-Regulated SMARCA4 Promotes Oral Squamous Cell Carcinoma Tumorigenesis.

机构信息

Department of Implantology, Stomatological Hospital of Xiamen Medical College & Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen 361008, China.

Engineering Research Center of Fujian University for Stomatological Biomaterials, Department of Stomatology, Xiamen Medical College, Xiamen 361023, China.

出版信息

Int J Mol Sci. 2023 Mar 1;24(5):4756. doi: 10.3390/ijms24054756.

Abstract

SWI/SNF related, matrix associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1), an ATPase subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, plays an important regulatory role in many cytogenetic and cytological processes during cancer development. However, the biological function and mechanism of SMARCA4 in oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to investigate the role of SMARCA4 in OSCC and its potential mechanism. Using a tissue microarray, SMARCA4 expression was found to be highly upregulated in OSCC tissues. In addition, SMARCA4 upregulate expression led to increased migration and invasion of OSCC cells in vitro, as well as tumor growth and invasion in vivo. These events were associated with the promotion of epithelial-mesenchymal transition (EMT). Bioinformatic analysis and luciferase reporter assay confirmed that SMARCA4 is a target gene of microRNA miR-199a-5p. Further mechanistic studies showed that the miR-199a-5p regulated SMARCA4 can promote the invasion and metastasis of tumor cells through EMT. These findings indicate that the miR-199a-5p- SMARCA4 axis plays a role in tumorigenesis by promoting OSCC cell invasion and metastasis through EMT regulation. Our findings provide insights into the role of SMARCA4 in OSCC and the mechanism involved, which may have important implications for therapeutic purposes.

摘要

SWI/SNF 相关、基质相关、肌动蛋白依赖性染色质调节因子亚家族 A 成员 4(SMARCA4,也称为 BRG1),是开关/蔗糖非发酵(SWI/SNF)染色质重塑复合物的 ATP 酶亚基,在癌症发展过程中的许多细胞遗传学和细胞学过程中发挥重要的调节作用。然而,SMARCA4 在口腔鳞状细胞癌(OSCC)中的生物学功能和机制尚不清楚。本研究旨在探讨 SMARCA4 在 OSCC 中的作用及其潜在机制。使用组织微阵列,发现 SMARCA4 在 OSCC 组织中高度上调。此外,SMARCA4 的上调表达导致 OSCC 细胞在体外的迁移和侵袭增加,以及体内肿瘤的生长和侵袭增加。这些事件与上皮-间充质转化(EMT)的促进有关。生物信息学分析和荧光素酶报告基因检测证实,SMARCA4 是 microRNA miR-199a-5p 的靶基因。进一步的机制研究表明,miR-199a-5p 调控的 SMARCA4 可以通过 EMT 促进肿瘤细胞的侵袭和转移。这些发现表明,miR-199a-5p-SMARCA4 轴通过 EMT 调节促进 OSCC 细胞的侵袭和转移,从而在肿瘤发生中发挥作用。我们的研究结果为 SMARCA4 在 OSCC 中的作用及其涉及的机制提供了新的见解,这可能对治疗目的具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15d2/10003091/3b93136a00f4/ijms-24-04756-g001.jpg

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