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NOP2/Sun RNA甲基转移酶4调控雷帕霉素哺乳动物靶标信号通路以促进肝细胞癌进展。

NOP2/Sun RNA Methyltransferase 4 Regulates the Mammalian Target of Rapamycin Signaling Pathway to Promote Hepatocellular Carcinoma Progression.

作者信息

Wang Congren, Ke Shaoying, Lin Shaoze, Lin Conglin, Cai Zhibing, Hong Lingju, Pan Qunxiong

机构信息

Department of Hepatobiliary Surgery, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.

出版信息

Turk J Gastroenterol. 2024 Nov 4;36(1):24-33. doi: 10.5152/tjg.2024.23684.

Abstract

BACKGROUND/AIMS: NOP2/Sun RNA methyltransferase 4 (NSUN4) is a prognostic indicator for hepatocellular carcinoma (HCC). However, the mechanism of NSUN4 in HCC is still unexplored. This project mainly focuses on the function and mechanism of NSUN4 in HCC malignant progression.

MATERIALS AND METHODS

The relation between the expression level of NSUN4 and the prognosis of HCC was measured by the means of bioinformatics. The expression level of NSUN4 was assessed by quantitative reverse transcription polymerase chain reaction. The western blot was utilized to determine the protein expression level of NSUN4 and mammalian target of rapamycin (mTOR) pathway-related proteins in cells and mouse tumor tissues. Cell counting kit-8 and colony formation assays were employed to measure cell proliferation ability. The wound healing assay and Transwell experiment were conducted to measure the cells' migration and invasion abilities. Flow cytometry was applied to determine the cell cycle.

RESULTS

NSUN4 was overexpressed in HCC tissues and cells, enhancing cell migration, proliferation, and invasion. The influence that NSUN4 exerted on HCC malignant progression could be reduced by the inhibitor of the mTOR pathway.

CONCLUSION

The study explained the mechanism and influence of NSUN4 on HCC progression by regulating the mTOR signaling pathway through in vitro and in vivo experiments, providing the theoretical basis and a new research direction for clinical prognostic prediction and treatment.

摘要

背景/目的:NOP2/Sun RNA甲基转移酶4(NSUN4)是肝细胞癌(HCC)的一个预后指标。然而,NSUN4在HCC中的作用机制仍未明确。本项目主要聚焦于NSUN4在HCC恶性进展中的功能及机制。

材料与方法

通过生物信息学方法检测NSUN4表达水平与HCC预后的关系。采用定量逆转录聚合酶链反应评估NSUN4的表达水平。利用蛋白质免疫印迹法测定细胞及小鼠肿瘤组织中NSUN4和雷帕霉素靶蛋白(mTOR)信号通路相关蛋白的表达水平。采用细胞计数试剂盒-8法和集落形成实验检测细胞增殖能力。进行伤口愈合实验和Transwell实验检测细胞迁移和侵袭能力。应用流式细胞术检测细胞周期。

结果

NSUN4在HCC组织和细胞中高表达,增强了细胞的迁移、增殖和侵袭能力。mTOR信号通路抑制剂可降低NSUN4对HCC恶性进展的影响。

结论

本研究通过体内外实验阐明了NSUN4通过调控mTOR信号通路影响HCC进展的机制,为临床预后预测和治疗提供了理论依据及新的研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45f3/11736862/98953e260bfe/tjg-36-1-24_f001.jpg

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