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emerin 敲低通过上调细胞质 p21 诱导肝癌细胞的迁移和侵袭。

Emerin knockdown induces the migration and invasion of hepatocellular carcinoma cells by up-regulating the cytoplasmic p21.

机构信息

Department of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, Jiangsu, China.

Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China.

出版信息

Neoplasma. 2022 Jan;69(1):59-70. doi: 10.4149/neo_2021_210728N1059. Epub 2021 Nov 4.

DOI:10.4149/neo_2021_210728N1059
PMID:34734530
Abstract

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.

摘要

emerin (EMD) 在细胞极性组织、核稳定性和细胞迁移等方面发挥着多样化的作用,然而,EMD 与肝细胞癌 (HCC) 细胞迁移和侵袭相关的生物学作用尚未阐明。在本研究中,我们初步发现 EMD 在 HCC 组织中上调,并且 EMD 表达与 HCC 细胞系自发转移潜能呈负相关。在 HCC 细胞中敲低 EMD 促进了细胞迁移和侵袭以及体内转移。同时,我们证明 EMD 敲低在 HCC 细胞中诱导 EMT 但增强了 p21 的表达。值得注意的是,在 HCC 细胞中沉默 EMD 增加了 p21 蛋白的细胞质定位,而 p21 敲低部分消除了由 EMD 敲低在 HCC 细胞中诱导的迁移和侵袭能力、EMT 和肌动蛋白细胞骨架重排。我们的研究结果表明 EMD 敲低在 HCC 细胞迁移和转移中起重要作用,通过上调细胞质中的 p21,揭示了 EMD 诱导细胞迁移调节的新机制。

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