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H3K27ac 诱导的 FOXC2-AS1 通过上调 E2F3 促进舌鳞状细胞癌的发生。

H3K27ac-induced FOXC2-AS1 accelerates tongue squamous cell carcinoma by upregulating E2F3.

机构信息

Department of Stomatology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

J Oral Pathol Med. 2021 Nov;50(10):1018-1030. doi: 10.1111/jop.13232. Epub 2021 Aug 17.

DOI:10.1111/jop.13232
PMID:34358374
Abstract

BACKGROUND

The important roles of lncRNAs have been reported in cancers, including tongue squamous cell carcinoma (TSCC). Here, we investigated the functional role and molecular mechanisms of lncRNA FOXC2-AS1 in TSCC.

METHODS

The expression level of FOXC2-AS1 in TSCC was determined by RT-qPCR. Its biological role was evaluated through colony formation assay, flow cytometry, wound healing, transwell, and Western blot analyses. The interactions among gene were tested by mechanistic investigations.

RESULTS

FOXC2-AS1 expression was high in TSCC tissues and cells. Functional assays in vitro showed that silencing FOXC2-AS1 restrained cell proliferation, cell cycle, migration, invasion, and EMT. In the mechanism, it was verified that H3K27 acetylation (H3K27ac) triggered an increase in FOXC2-AS1 expression. Furthermore, FOXC2-AS1 was identified as a cytoplasmic lncRNA and served as a ceRNA to upregulate E2F3 expression via sponging miR-6868-5p.

CONCLUSION

H3K27ac-induced FOXC2-AS1 exhibits carcinogenic property in TSCC by the miR-6868-5p/E2F3 axis.

摘要

背景

长链非编码 RNA(lncRNA)在癌症中具有重要作用,包括舌鳞状细胞癌(TSCC)。在这里,我们研究了 lncRNA FOXC2-AS1 在 TSCC 中的功能作用和分子机制。

方法

通过 RT-qPCR 测定 TSCC 中 FOXC2-AS1 的表达水平。通过集落形成实验、流式细胞术、划痕愈合、Transwell 分析和 Western blot 分析评估其生物学作用。通过机制研究测试基因之间的相互作用。

结果

FOXC2-AS1 在 TSCC 组织和细胞中表达较高。体外功能实验表明,沉默 FOXC2-AS1 抑制细胞增殖、细胞周期、迁移、侵袭和 EMT。在机制上,验证了 H3K27 乙酰化(H3K27ac)引发 FOXC2-AS1 表达增加。此外,FOXC2-AS1 被鉴定为细胞质 lncRNA,通过海绵 miR-6868-5p 上调 E2F3 表达。

结论

H3K27ac 诱导的 FOXC2-AS1 通过 miR-6868-5p/E2F3 轴在 TSCC 中表现出致癌特性。

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