现代检验医学杂志2026，Vol.41Issue(2)：174-180,7.DOI:10.3969/j.issn.1671-7414.2026.02.029
基于TCGA数据库生物学信息分析FEN1与肺腺癌相关性并敲低FEN1基因抑制小鼠Lewis肺癌细胞生长及其分子机制的实验研究
TCGA-Based Analysis of FEN1 in Lung Adenocarcinoma and the Molecular Mechanism of FEN1 Knockdown Inhibiting the Growth of Lewis Lung Cancer Cells in Mice
摘要
Abstract
Objective To analyze the expression characteristics and prognostic value of Flap Endonuclease 1(FEN1)in lung ad-enocarcinoma based on The Cancer Genome Atlas(TCGA)database and elucidate the molecular mechanisms by which FEN1 regulates the biological behavior of lung cancer cells.Methods Transcriptomic data from 598 samples(539 lung adenocarcino-ma tissues and 59 normal tissues)in the TCGA database were analyzed to evaluate the relationship between FEN1 expression and patient prognosis.Lewis lung carcinoma(LLC)cells with FEN1 knockdown were established and divided into LLC group,shRNA-NC group,and FEN1-shRNA group based on transfection status.Cell proliferation,apoptosis,cell cycle progression,mi-gration and invasion abilities were detected using CCK-8 assay,flow cytometry and Transwell assay,respectively.The expression of epithelial-mesenchymal transition(EMT)markers(E-cadherin,N-cadherin,Vimentin)and cell cycle protein Cyclin D1,Bcl-2 and MMP9 were measured by RT-qPCR and Western blot.Results FEN1 was highly expressed in lung adenocarcinoma tissues and significantly correlated with poor prognosis(Log-rank test,Z=2.81,P=0.005).A stable FEN1 knockdown cell lines were suc-cessfully constructed with a knockdown efficiency of 83.8％.Compared with LLC groups,the survival rates of FEN1-shRNA group at 24h and 48h decreased[(62.31±2.84)％vs(100.00±0.93)％and[(81.58±2.35)％vs(100.00±4.88)％],while the apoptosis rate increased to[(25.82±0.30)％vs(3.19±0.46)％],and the differences were statistically significant(t=30.892,8.336,-70.889,all P＜0.001).Cell cycle was arrested at S phase with the S phase proportion increased to[(71.07±3.27)％vs(47.85±4.15)％](F=43.688,P＜0.001).The number of migrated cells(118.556±12.738 vs 192.222±14.986)and invaded cells(92.667±3.000 vs 129.000±9.042)were significantly decreased,and the differences were statistically significant(t=6.487,6.606,all P＜0.001).Molecular mechanism analysis revealed that FEN1 knockdown reversed the EMT process:E-cadherin pro-tein and mRNA were upregulated(t=-10.478,-4.235),while N-cadherin,Vimentin,Cyclin D1,Bcl-2,and MMP9 protein and mRNA were all downregulated(t=-20.825～33.396),and the differences were statistically significant(all P＜0.05).Conclusions FEN1 is highly expressed in lung adenocarcinoma and associates with poor prognosis.FEN1 promotes the malignant phenotypes of lung cancer cells by regulating the EMT pathway.FEN 1 knockdown inhibits cell proliferation,migration and invasion while promoting apoptosis,suggesting that FEN1 can serve as an important biomarker for prognostic assessment and a potential thera-peutic target for lung adenocarcinoma.关键词
瓣状核酸内切酶1/肺腺癌/路易斯肺癌细胞/上皮-间充质转化/细胞凋亡Key words
flap endonuclease 1/lung adenocarcinoma/Lewis lung cancer cells/epithelial-mesenchymal transition/apoptosis分类
医药卫生引用本文复制引用
沈志勇,王玲,朱正安,林秀华,傅志超,陈忠华..基于TCGA数据库生物学信息分析FEN1与肺腺癌相关性并敲低FEN1基因抑制小鼠Lewis肺癌细胞生长及其分子机制的实验研究[J].现代检验医学杂志,2026,41(2):174-180,7.基金项目
福建省自然科学基金项目(2023J011360). （2023J011360）
