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KIAA1522通过激活Wnt/β-连环蛋白信号通路促进肝细胞癌进展。

KIAA1522 Promotes the Progression of Hepatocellular Carcinoma via the Activation of the Wnt/β-Catenin Signaling Pathway.

作者信息

Jiang Shunbin, Zhang Yonggang, Li Qing, Qiu Lei, Bian Baoxiang

机构信息

Department of Imaging, Lianyungang No 1 People's Hospital, Lianyungang, People's Republic of China.

School of Medicine, Southeast University, Nanjing, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 16;13:5657-5668. doi: 10.2147/OTT.S251157. eCollection 2020.

Abstract

PURPOSE

was previously identified to play a crucial role in cancer development and progression. However, its functions and underlying mechanisms in hepatocellular carcinoma (HCC) remain elusive.

MATERIALS AND METHODS

To elucidate the role of in HCC, its expression was assessed using The Cancer Genome Atlas and GEPIA databases. Next, these results were validated by quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry of HCC tissues and cell lines. Flow cytometry, CCK-8, EDU, colony formation, Transwell invasion, and wound healing assays were performed to explore the function of in HCC in vivo and in vitro. Finally, gene set enrichment analysis was used to identify the pathways involved.

RESULTS

Our results demonstrated that was highly expressed in HCC tissues and cell lines. Furthermore, overexpression was associated with unfavorable clinicopathological characteristics. Survival analyses revealed that overexpression predicted lower recurrence-free and overall survival rates in patients with HCC. Functional studies suggested that facilitated HCC proliferation, migration, and invasion both in vitro and in vivo. Moreover, up-regulated the Wnt/β-catenin signaling pathway, as confirmed by TOP-flash/FOP-flash luciferase reporter assays and Western blotting.

CONCLUSION

In conclusion, we highlighted the oncogenic role of in HCC and determined its potential as a therapeutic target for HCC.

摘要

目的

先前已确定其在癌症发展和进展中起关键作用。然而,其在肝细胞癌(HCC)中的功能和潜在机制仍不清楚。

材料与方法

为阐明其在HCC中的作用,使用癌症基因组图谱和GEPIA数据库评估其表达。接下来,通过定量逆转录-聚合酶链反应、蛋白质免疫印迹法以及HCC组织和细胞系的免疫组织化学对这些结果进行验证。进行流式细胞术、CCK-8、EDU、集落形成、Transwell侵袭和伤口愈合试验,以探究其在体内和体外HCC中的功能。最后,使用基因集富集分析来确定所涉及的途径。

结果

我们的结果表明,其在HCC组织和细胞系中高表达。此外,其过表达与不良的临床病理特征相关。生存分析显示,其过表达预示着HCC患者较低的无复发生存率和总生存率。功能研究表明,其在体外和体内均促进HCC的增殖、迁移和侵袭。此外,通过TOP-flash/FOP-flash荧光素酶报告基因试验和蛋白质免疫印迹法证实,其上调了Wnt/β-连环蛋白信号通路。

结论

总之,我们强调了其在HCC中的致癌作用,并确定了其作为HCC治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a727/7305824/5ff3555d7b86/OTT-13-5657-g0001.jpg

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