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腺瘤性结肠息肉病结合蛋白末端结合蛋白 1 促进肝癌生长和转移。

Adenomatous polyposis coli-binding protein end-binding 1 promotes hepatocellular carcinoma growth and metastasis.

机构信息

Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.

出版信息

PLoS One. 2020 Sep 21;15(9):e0239462. doi: 10.1371/journal.pone.0239462. eCollection 2020.

Abstract

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.

摘要

本研究旨在确定腺瘤性结肠息肉病基因(APC)结合蛋白末端结合蛋白 1(EB1)在肝细胞癌(HCC)中的临床意义,并与之前的报道相比,对其生化作用进行特征描述。我们通过免疫组织化学染色检测了 235 例 HCC 患者组织中的 EB1 表达情况,并研究了其与临床病理特征和预后的相关性。我们还通过 siRNA 和 CRISPR/Cas9 介导的 EB1 表达在人 HCC 细胞系中的调控,研究了 EB1 在细胞增殖、迁移和肿瘤发生中的作用。结果表明,EB1 表达与几个与肿瘤恶性程度相关的重要因素显著相关,包括组织学分化、门静脉侵犯状态和肝内转移。HCC 组织中 EB1 表达较高的患者总体生存率和复发率均低于 EB1 表达较低的患者。在 HCC 细胞中敲低和敲除 EB1 可降低细胞增殖、迁移和侵袭能力,并抑制体内肿瘤生长。此外,通过 RNA 微阵列分析鉴定出与 EB1 差异表达相关的编码 Dlk1、HAMP 和 SLCO1B3 的基因。综上所述,EB1 的高表达促进了 HCC 的肿瘤生长和转移。EB1 可作为 HCC 的新生物标志物,与 EB1 共表达的基因可能代表潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/451c/7505586/9cb1ae92bb8a/pone.0239462.g001.jpg

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