miR-2053 的下调通过靶向 Fyn 相关激酶（FRK）抑制食管癌细胞的发展和进展。
Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK).
机构信息
Department of Thoracic Surgery, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun City, 130041, Jilin Province, People's Republic of China.
Department of Anesthesiology, The Second Hospital of Jilin University, Changchun City, 130041, Jilin Province, People's Republic of China.
出版信息
Dig Dis Sci. 2020 Oct;65(10):2853-2862. doi: 10.1007/s10620-019-06015-5. Epub 2020 Jan 1.
BACKGROUND
MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of cancers including esophageal carcinoma (ESCA). Increasing numbers of miRNAs have been identified to be important regulators in the progression of ESCA by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in ESCA need sufficient elucidation.
AIMS
In the present study, the function of miR-2053 was investigated in ESCA cells.
METHODS
The expression of miR-2053 was detected in four different ESCA cell lines (Eca109, Ec9706, KYSE30, and TE-1 cells) and normal cell line (HEEC) by qRT-PCR. Cell proliferation, migration, and invasion abilities after knockdown of miR-2053 were assessed by CCK-8 assay, scratch assay, and transwell assay, respectively. Cell cycle of ESCA cells was detected by flow cytometric analysis. Expression of proteins in ESCA cells was detected by Western blot analysis.
RESULTS
The results showed that the expression of miR-2053 was remarkably up-regulated in ESCA tissues and cells lines. Down-regulation of miR-2053 markedly inhibited cell proliferation, migration, and invasion and markedly induced cell cycle arrest and cell apoptosis in ESCA cell lines. Fyn-related kinase (FRK) was a target gene of miR-2053. Moreover, down-regulation of miR-2053 mediated the protein kinase B (AKT)/mammalian target of rapamycin and Wnt3a/β-catenin signaling pathway in ESCA cell lines.
CONCLUSIONS
Our results together suggest the potential of regulating miR-2053 expression against development and progression of esophageal carcinoma by targeting FRK.
背景
微小 RNA（miRNAs）在各种类型的癌症的调控和病理生理学中发挥着重要作用，包括食管癌（ESCA）。越来越多的 miRNA 被鉴定为 ESCA 进展中的重要调控因子，通过调节基因表达。然而，功能 miRNA 及其在 ESCA 中的潜在机制仍需要充分阐明。
目的
本研究旨在探讨 miR-2053 在 ESCA 细胞中的作用。
方法
通过 qRT-PCR 检测四种不同的 ESCA 细胞系（Eca109、Ec9706、KYSE30 和 TE-1 细胞）和正常细胞系（HEEC）中 miR-2053 的表达。通过 CCK-8 测定、划痕实验和 Transwell 测定分别评估 miR-2053 敲低后 ESCA 细胞的增殖、迁移和侵袭能力。通过流式细胞术分析检测 ESCA 细胞的细胞周期。通过 Western blot 分析检测 ESCA 细胞中蛋白质的表达。
结果
结果表明，miR-2053 在 ESCA 组织和细胞系中表达显著上调。下调 miR-2053 显著抑制 ESCA 细胞系的增殖、迁移和侵袭，并显著诱导细胞周期停滞和细胞凋亡。Fyn 相关激酶（FRK）是 miR-2053 的靶基因。此外，下调 miR-2053 介导了 ESCA 细胞系中的蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白和 Wnt3a/β-连环蛋白信号通路。
结论
我们的研究结果表明，通过靶向 FRK，调节 miR-2053 的表达可能成为抑制食管癌发展和进展的潜在手段。
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