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DAL-1 通过抑制非小细胞肺癌中 HSPA5 的表达来减弱上皮间质转化和转移。

DAL-1 attenuates epithelial to mesenchymal transition and metastasis by suppressing HSPA5 expression in non-small cell lung cancer.

机构信息

Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Xinzao, Panyu, Guangzhou, Guangdong 511436, P.R. China.

出版信息

Oncol Rep. 2017 Nov;38(5):3103-3113. doi: 10.3892/or.2017.6000. Epub 2017 Sep 26.

Abstract

Metastasis is the primary cause of death in lung cancer patients and EMT (epithelial-mesenchymal transition) promotes metastasis. Previous study revealed that DAL-1 (differentially expressed in adenocarcinoma of the lung) could attenuate EMT and metastasis in non-small cell lung cancer (NSCLC). Further study proved that HSPA5 (heat shock protein 5), which has a promoting effect on EMT, could bind to DAL-1. In this study, the mRNA and protein expression levels of target molecules were detected by RTq-PCR and western blot assays, the migration and invasion abilities were examined by Transwell migration and invasion assay, and the proliferation ability was measured by CCK-8 assay. We revealed that DAL-1 was downregulated while HSPA5 was upregulated in NSCLC and found the protein of DAL-1 and HSPA5 co-localized in the cytoplasm and nucleus. We demonstrated that DAL-1 can suppress the expression of HSPA5 on mRNA and protein levels, and decrease EMT, migration, invasion and proliferation abilities by down-regulating HSPA5. Furthermore, we discovered that DAL-1 plays a role in inhibiting PI3K/Akt/Mdm2 signaling pathway by suppressing HSPA5.

摘要

转移是肺癌患者死亡的主要原因,而 EMT(上皮间质转化)促进转移。先前的研究表明,DAL-1(肺癌腺癌差异表达)可以减弱非小细胞肺癌(NSCLC)中的 EMT 和转移。进一步的研究证明,具有 EMT 促进作用的 HSPA5(热休克蛋白 5)可以与 DAL-1 结合。在这项研究中,通过 RTq-PCR 和 Western blot 检测靶分子的 mRNA 和蛋白表达水平,通过 Transwell 迁移和侵袭实验检测迁移和侵袭能力,通过 CCK-8 实验检测增殖能力。我们揭示了 NSCLC 中 DAL-1 下调而 HSPA5 上调,并发现 DAL-1 和 HSPA5 的蛋白在细胞质和核中共定位。我们证明 DAL-1 可以通过下调 HSPA5 抑制 HSPA5 在 mRNA 和蛋白水平上的表达,降低 EMT、迁移、侵袭和增殖能力。此外,我们发现 DAL-1 通过抑制 HSPA5 发挥抑制 PI3K/Akt/Mdm2 信号通路的作用。

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