胞质多聚腺苷酸结合蛋白4在肝癌中的表达及其功能

doi:10.3969/j.issn.1004-616x.2025.03.006

癌变·畸变·突变 ›› 2025, Vol. 37 ›› Issue (3): 209-214,220.doi: 10.3969/j.issn.1004-616x.2025.03.006

• 论著 • 上一篇

胞质多聚腺苷酸结合蛋白4在肝癌中的表达及其功能

刘鑫苗¹, 高红军², 康艳³, 张赟¹, 孙玉琳¹

1. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学全国重点实验室, 北京 100021;
2. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 检验科, 北京 100021;
3. 山西省肿瘤医院/中国医学科学院肿瘤医院山西医院/山西医科大学附属肿瘤医院, 检验科, 山西太原 030013

收稿日期:2025-03-27 修回日期:2025-04-23 发布日期:2025-06-13
通讯作者: 孙玉琳
作者简介:刘鑫苗，E-mail：liuxinmiao2103@163.com。
基金资助:
国家自然科学基金(82073327)；中国医学科学院医学与健康科技创新工程(2021-I2M-1-066)

Expression and function of PABPC4 in liver cancers

LIU Xinmiao¹, GAO Hongjun², KANG Yan³, ZHANG Yun¹, SUN Yulin¹

1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021;
2. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021;
3. Department of Clinical Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, Shanxi, China

Received:2025-03-27 Revised:2025-04-23 Published:2025-06-13

摘要/Abstract

摘要： 目的：探讨胞质多聚腺苷酸结合蛋白4(PABPC4)在肝癌组织中的表达特征和预后意义，及其对肝癌细胞生物学行为的影响。方法：下载癌症基因组图谱(TCGA)中的肝癌RNA测序数据，分析PABPC4 mRNA表达与患者预后的关系；分别构建PABPC4敲降和过表达的肝癌细胞系，采用实时定量PCR和Western blot检测细胞中PABPC4及干性相关指标mRNA和蛋白的表达，通过CCK-8 法、平板集落形成实验、细胞划痕实验、Transwell 实验等研究 PABPC4 对细胞增殖、迁移、侵袭及干性的影响。结果：TCGA数据库分析结果显示，肝癌组织中PABPC4 mRNA的表达水平随病理分级的增加而逐渐升高，高表达PABPC4 mRNA的患者其总生存时间和无复发生存时间较短(P<0.05)，PABPC4 mRNA表达水平可作为独立的预后风险因素，高表达PABPC4 mRNA的肿瘤组织中Wnt信号通路相关蛋白上调并显著富集。本研究成功构建了PABPC4稳定敲降的HLF细胞和稳定过表达的Huh7细胞，功能实验表明，与对照组相比，敲降PABPC4可显著抑制细胞增殖、迁移、侵袭和集落形成能力(P<0.05)；过表达PABPC4后的作用相反(P<0.05)。此外高表达PABPC4后，细胞干性相关指标(Nanog、OCT4、CD133、SOX2)的mRNA表达水平均较对照组升高(P<0.05或P<0.01)。结论：PABPC4在肝癌中高表达且与不良预后相关，可作为肝癌的独立预后指标。其高表达可增强癌细胞的干性，促进肝癌细胞的增殖、存活、迁移和侵袭等恶性表型，有望成为有潜力的肝癌预后预测和治疗干预靶点。

关键词: 肝癌, 胞质多聚腺苷酸结合蛋白4, 预后预测, 增殖存活, 迁移侵袭, 细胞干性

Abstract: OBJECTIVE： To investigate the expression characteristics， prognostic significance and functional role of cytoplasmic polyadenylate-binding protein 4 (PABPC4) in liver cancers. METHODS： RNA sequencing data of liver cancers from The Cancer Genome Atlas (TCGA) were downloaded to analyze relationships between PABPC4 expression and patient prognosis. PABPC4 knockdown and overexpression liver cancer cell lines were constructed， and expression of PABPC4， its stemness-related indexes mRNA and protein in cells were detected by real-time quantitative PCR and Western blot. Effects of PABPC4 on cell proliferation，migration，invasion and stemness were studied by CCK-8 method，plate colony formation assay， cell scratch assay and Transwell assay. RESULTS： Expression levels of PABPC4 in liver cancer tissues gradually increased with increase of pathological grade. Patients with high expression had shorter overall survival and recurrence-free survival time (P<0.05). In tumor tissues with the high expression showed upregulated PABPC4，Wnt signaling pathway-related proteins. The successfully constructed HLF cells showed stable knockdown of PABPC4 and Huh7 cells with stable overexpression. Functional experiments showed that knockdown of PABPC4 showed significantly inhibited cell proliferation， migration， invasion and colony formation (P<0.05). Overexpression of PABPC4 had the opposite effect (P<0.05). In addition， after high expression of PABPC4， the mRNA expression levels of cell stemness-related indicators (Nanog， OCT4， CD133， SOX2) were significantly increased. CONCLUSION： PABPC4 was highly expressed and was correlated with poor prognosis in liver cancer patients. PABPC4 enhanced cancer cell stemness and promoted proliferation， survival， migration， and invasion of cancer cells. Therefore， PABPC4 is a potential target for prognostic prediction and therapeutic intervention in liver cancer.

Key words: liver cancer, PABPC4, prognostic prediction, proliferation and survival, migration and invasion, cell stemness

中图分类号:

R735.7

刘鑫苗, 高红军, 康艳, 张赟, 孙玉琳. 胞质多聚腺苷酸结合蛋白4在肝癌中的表达及其功能[J]. 癌变·畸变·突变, 2025, 37(3): 209-214,220.

LIU Xinmiao, GAO Hongjun, KANG Yan, ZHANG Yun, SUN Yulin. Expression and function of PABPC4 in liver cancers[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(3): 209-214,220.

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胞质多聚腺苷酸结合蛋白4在肝癌中的表达及其功能

Expression and function of PABPC4 in liver cancers

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