安徽医科大学安徽省第二人民医院临床学院普外科;安徽医科大学第五临床医学院;安徽省第二人民医院职业健康安徽省重点实验室;安徽省第二人民医院普外科;安徽医科大学临床医学院外科学教研室;
目的 探讨PPFIA4在肝细胞癌组织和HCCLM3细胞中的表达水平及其对肝细胞癌生物学行为的调控。方法 选择生物信息学分析、Western blot法和免疫组化法检测肝细胞癌患者肿瘤组织中PPFIA4表达情况并进行患者预后的相关分析；设计siRNA质粒瞬转敲低HCCLM3细胞中PPFIA4表达，选取划痕愈合实验和Transwell实验检测敲低PPFIA4对HCCLM3细胞迁移、侵袭能力的影响；借助Western blot法检测HCCLM3细胞株转染siRNA质粒后上皮-间充质转化(EMT)相关蛋白标志物的表达变化。结果 PPFIA4在肝细胞癌组织和肝细胞癌细胞(HCCLM3、Li-7、MHCC97H)中高表达；PPFIA4高表达提示患者临床分期较晚，总体生存期(OS)较短；敲低HCCLM3细胞株中PPFIA4表达后，HCCLM3细胞迁移和侵袭能力均下降(P<0.001),并且EMT标志物表达发生变化，上皮细胞标志物E-cadherin的表达增加(P<0.01),而间充质标志物Vimentin、N-cadherin的表达下降(P<0.05、P<0.01)。结论 PPFIA4在肝细胞癌组织和肝癌细胞株中呈高表达并与患者不良预后相关，沉默PPFIA4后能够调控肝癌细胞生物学行为，抑制HCCLM3细胞迁移和侵袭能力，其具体机制可能与EMT相关。
| 111 | 0 | 36 |
| 下载次数 | 被引频次 | 阅读次数 |
[1] Sung H,Ferlay J,Siegel R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-49.doi:10.3322/caac.21660.
[2] Xia C,Dong X,Li H,et al.Cancer statistics in China and United States,2022:profiles,trends,and determinants[J].Chin Med J (Engl),2022,135(5):584-90.doi:10.1097/CM9.0000000000002108.
[3] Sun Q,Wang H,Xiao B,et al.Development and validation of a 6-gene hypoxia-related prognostic signature for cholangiocarcinoma[J].Front Oncol,2022,12:954366.doi:10.3389/fonc.2022.954366.
[4] Zheng F X,Yang C R,Sun F Y,et al.Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression[J].J Biochem Mol Toxicol,2024,38(6):e23746.doi:10.1002/jbt.23746.
[5] Fu F,Niu R,Zheng M,et al.Clinicopathological significances and prognostic value of PPFIA4 in colorectal cancer[J].J Cancer,2023,14(1):24-34.doi:10.7150/jca.78634.
[6] Gao Y,Guan L,Jia R,et al.High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis[J].BMC Cancer,2023,23(1):417.doi:10.1186/s12885-023-10872-9.
[7] Chu J,Min K W,Kim D H,et al.High PPFIA1 expression promotes cancer survival by suppressing CD8+ T cells in breast cancer:drug discovery and machine learning approach[J].Breast Cancer,2023,30(2):259-70.doi:10.1007/s12282-022-01419-0.
[8] 严洪遥，劳远翔，孙倍成.UROC1在肝细胞癌中的表达及对肿瘤发生的影响[J].安徽医科大学学报，2024,59(8):1339-46.doi:10.19405/j.cnki.issn1000-1492.2024.08.008.[8] Yan H Y,Lao Y X,Sun B C.Expression of UROC1 in hepatocellular carcinoma and its effect on tumor development[J].Acta Univ Med Anhui,2024,59(8):1339-46.doi:10.19405/j.cnki.issn1000-1492.2024.08.008.
[9] Yamasaki A,Nakayama K,Imaizumi A,et al.Liprin-α4 as a possible new therapeutic target for pancreatic cancer[J].Anticancer Res,2017,37(12):6649-54.doi:10.21873/anticanres.12122.
[10] Onishi H,Yamasaki A,Nakamura K,et al.Liprin-α4 as a new therapeutic target for SCLC as an upstream mediator of HIF1α[J].Anticancer Res,2019,39(3):1179-84.doi:10.21873/anticanres.13227.
[11] Zhao R,Feng T,Gao L,et al.PPFIA4 promotes castration-resistant prostate cancer by enhancing mitochondrial metabolism through MTHFD2[J].J Exp Clin Cancer Res,2022,41(1):125.doi:10.1186/s13046-022-02331-3.
[12] Huang J,Yang M,Liu Z,et al.PPFIA4 promotes colon cancer cell proliferation and migration by enhancing tumor glycolysis[J].Front Oncol,2021,11:653200.doi:10.3389/fonc.2021.653200.
[13] Tan S,Yu H,Xu Y,et al.Hypoxia-induced PPFIA4 accelerates the progression of ovarian cancer through glucose metabolic reprogramming[J].Med Oncol,2023,40(9):272.doi:10.1007/s12032-023-02144-0.
[14] Huang Y,Hong W,Wei X.The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis[J].J Hematol Oncol,2022,15(1):129.doi:10.1186/s13045-022-01347-8.
基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.03.005
中图分类号:R735.7
引用信息:
[1]崔浩东,殷济民,郭凯等.PPFIA4基因在肝细胞癌中的表达及作用机制[J].安徽医科大学学报,2025,60(03):414-421.DOI:10.19405/j.cnki.issn1000-1492.2025.03.005.
基金信息:
安徽省重点研究与开发计划人口健康专项项目(编号：202104j07020005); 安徽省高校自然科学研究项目(编号：2023AH010084、2022AH052030)~~