中文版 | English
Title

NF-YA/CDCA8轴通过调控MAPK信号通路促进肝癌的进展

Alternative Title
NF-YA/CDCA8 axis promotes HCC progression by regulating MAPK signaling pathway
Author
Name pinyin
HE Yu
School number
11930143
Degree
硕士
Discipline
0710 生物学
Subject category of dissertation
07 理学
Supervisor
张健
Mentor unit
南方科技大学医学院
Publication Years
2022-04-27
Submission date
2022-06-29
University
南方科技大学
Place of Publication
深圳
Abstract

       肝癌是最常见的消化道癌症之一。高达三分之二的患者首次被诊断即为癌症中晚期。患者即使接受手术,术后也很快复发和转移。因此,深入研究肝癌的发生发展和转移机制,探索肝癌恶性演进的标志物是当前肝癌研究领域的重点。
       细胞分裂周期相关8(CDCA8)基因是脊椎动物染色体乘客复合物的重要组成部分,它在多种肿瘤中高表达并促进肿瘤进展。然而,目前CDCA8在肝癌中的作用机制尚不完全清楚。本研究旨在通过分析CDCA8的表达与肝癌细胞增殖和转移的关系,揭示CDCA8在肝癌中的作用,并探索及其上下游信号通路。我们在收集的临床标本中验证了CDCA8在肝癌组织中的表达显著高于癌旁组织。通过TCGA数据库我们发现CDCA8在肝癌中高表达,并且CDCA8的高表达与肝癌患者不良预后显著相关。免疫组织化学染色实验证实CDCA8的高表达也提示与患者较短的总生存期和无病生存期相关。通过CCK8细胞增殖实验、克隆形成实验、细胞迁移和侵袭实验,我们发现敲低CDCA8的表达可以抑制PLC/PRF/5和HepG2等肝癌细胞的体外增殖和浸润。裸鼠皮下瘤以及尾静脉肺转移瘤模型实验结果提示CDCA8促进肝癌细胞在裸鼠体内的生长和肺部转移。
       在此基础上,针对敲低CDCA8的细胞系进行RNA测序,结果提示CDCA8多个下游潜在靶点。细胞系验证得到NECAP2、TPM3和USP13是CDCA8关系最为密切相关的下游分子,数据库分析提示这三个基因与患者不良预后呈显著相关; 富集分析显示,CDCA8的表达可能影响MAPK信号通路。蛋白印迹实验进一步验证了CDCA8促进MEK/ERK的磷酸化发挥促癌效应。此外,我们通过生信分析以及实验验证转录因子NF-YA可能是调控CDCA8的上游基因,更为重要的是,干扰CDCA8可以逆转NF-YA的促癌作用。综上,本研究发现NF-YA/CDCA8信号轴通过激化MEK/ERK磷酸化促进肝癌增殖转移。

 

Keywords
Language
Chinese
Training classes
独立培养
Enrollment Year
2019
Year of Degree Awarded
2022-07
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Academic Degree Assessment Sub committee
医学院
Domestic book classification number
Q291
Data Source
人工提交
Document TypeThesis
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/343159
DepartmentSchool of Medicine
Recommended Citation
GB/T 7714
贺宇. NF-YA/CDCA8轴通过调控MAPK信号通路促进肝癌的进展[D]. 深圳. 南方科技大学,2022.
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11930143-贺宇-南方科技大学医学(5649KB) Embargo--2023-6-29后可获取Fulltext Requests
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