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Lnc524369通过激活YWHAZ-RAF1信号通路促进肝细胞癌进展并预示不良预后。

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling.

作者信息

Zheng Wei, Shen Guo-Liang, Xu Ke-Yang, Yin Qiao-Qiao, Hui Tian-Chen, Zhou Zhe-Wen, Xu Cheng-An, Wang Shou-Hao, Wu Wen-Hao, Shi Ling-Fei, Pan Hong-Ying

机构信息

Department of Clinical Medicine, Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.

Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China.

出版信息

World J Gastrointest Oncol. 2022 Jan 15;14(1):253-264. doi: 10.4251/wjgo.v14.i1.253.

Abstract

BACKGROUND

Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear.

AIM

To explore the function of Lnc524369 in HCC.

METHODS

To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis.

RESULTS

Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time.

CONCLUSION

Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

摘要

背景

肝癌是恶性程度最高的癌症之一,具有易转移和放化疗耐药的特点。新出现的证据表明,包括Lnc524369在内的长链非编码RNA(LncRNAs)高度参与肝细胞癌(HCC)的发生、发展、放疗抵抗和化疗抵抗。然而,Lnc524369的功能仍不清楚。

目的

探讨Lnc524369在肝癌中的作用。

方法

为研究Lnc524369的作用,采用CCK8、迁移和侵袭实验分析了41例肝癌患者的组织。通过qPCR检测肝癌细胞系和人肝癌组织中的Lnc524369和YWHAZ(也称为14-3-3ζ)mRNA,通过蛋白质印迹法检测YWHAZ和RAF1蛋白。使用癌症细胞系百科全书(CCLE)数据库、STRING数据库、人类蛋白质图谱数据库和TCGA数据库进行生物信息学分析。

结果

Lnc524369在肝癌细胞核和人肝癌组织中显著上调。Lnc524369的过表达与肝癌细胞的增殖、迁移和侵袭有关。YWHAZ和RAF1蛋白以及YWHAZ mRNA在肝癌中过表达,Lnc524369的过表达可使其减弱。Lnc524369及其下游靶点YWHAZ和RAF1蛋白与总生存时间呈负相关。

结论

Lnc524369可能是肝癌的一个有前景的靶点,因为它可通过激活YWHAZ/RAF1途径促进肝癌进展并缩短肝癌患者的总生存时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1db8/8790426/e792d6f4d2c2/WJGO-14-253-g001.jpg

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