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通过 miR-194/GRHL3/PTEN/Akt 轴促进食管鳞癌细胞的增殖和迁移。

Promotes the Proliferation and Migration of Esophageal Squamous Cell Carcinoma through the miR-194/GRHL3/PTEN/Akt Axis.

出版信息

ACS Infect Dis. 2020 May 8;6(5):871-881. doi: 10.1021/acsinfecdis.0c00007. Epub 2020 Apr 23.

DOI:10.1021/acsinfecdis.0c00007
PMID:32298082
Abstract

Recent studies have revealed that is closely related to the occurrence and progression of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism of in ESCC has not been well elucidated. To explore the mechanism of infection in ESCC, cellular proliferation, invasion, and migration models of KYSE-30 and KYSE-150 cells infected by at a multiplicity of infection (MOI) of 10 were established. The results showed that infection could drastically increase the proliferation, invasion, and migration ability of ESCC. Furthermore, the results of high-throughput sequencing showed that miR-194 was considerably upregulated in infected cells compared with control cells, which was further verified by qRT-PCR. The inhibition or overexpression of miR-194 had a significant effect on KYSE-30 and KYSE-150 cell migration and invasion. Additionally, the levels of GRHL3 and PTEN were decreased in -infected esophageal cancer cells compared with uninfected esophageal cancer cells. Furthermore, dual-luciferase experiments confirmed that GRHL3 is a direct target of miR-194. In addition, the GRHL3-related pathway was investigated, and the levels of GRHL3 and PTEN were downregulated while the level of p-Akt was upregulated after infection. Taken together, these findings indicated that might promote ESCC proliferation and migration via the miR-194/GRHL3/PTEN/Akt signaling axis.

摘要

最近的研究表明, 与食管鳞状细胞癌(ESCC)的发生和发展密切相关。然而, 在 ESCC 中的作用机制尚未得到充分阐明。为了探讨 感染在 ESCC 中的机制,建立了感染复数(MOI)为 10 的 KYSE-30 和 KYSE-150 细胞的细胞增殖、侵袭和迁移模型。结果表明, 感染可显著增加 ESCC 的增殖、侵袭和迁移能力。此外,高通量测序结果显示,与对照细胞相比,感染细胞中 miR-194 显著上调,qRT-PCR 进一步验证了这一点。miR-194 的抑制或过表达对 KYSE-30 和 KYSE-150 细胞的迁移和侵袭有显著影响。此外,与未感染的食管癌细胞相比,感染 的食管癌细胞中 GRHL3 和 PTEN 的水平降低。此外,双荧光素酶实验证实 GRHL3 是 miR-194 的直接靶标。此外,还研究了 GRHL3 相关通路,结果显示, 感染后 GRHL3 和 PTEN 的水平下调,而 p-Akt 的水平上调。综上所述,这些发现表明, 通过 miR-194/GRHL3/PTEN/Akt 信号通路, 可能促进 ESCC 的增殖和迁移。

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