| 147 | 0 | 95 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨转录因子ZNF174在非小细胞肺癌(NSCLC)中对肿瘤干性的影响。方法 通过StemChecker在线分析ZNF174对肿瘤干性指标影响；酶切酶联构建ZNF174敲低质粒；同源重组构建ZNF174过表达质粒；慢病毒感染构建ZNF174敲低和过表达细胞稳系；肿瘤干细胞成球检测干性维持能力；RNA-seq和实时荧光定量PCR(qPCR)检测对关键干性基因表达的影响。结果 转录因子ZNF174在NSCLC中对细胞干性中起促进作用，促进肿瘤干性基因：原癌基因B细胞特异性小鼠白血病病毒插入位点1(BMI1)、乙醛脱氢酶2(ALDH2)、性别决定区Y-框2(SOX2)、高迁移率族蛋白A2(HMGA2)和蜗牛家族转录抑制因子1(Snail1)表达，并促进NSCLC肿瘤干细胞成球。结论 ZNF174在NSCLC中促进肿瘤干性，具有成为NSCLC治疗和预后评估新靶点的潜力。
Abstract：Objective To explore the effect of transcription factor ZNF174 on the stemness of non-small cell lung cancer(NSCLC). Methods StemChecker online analysis was employed to assess the impact of ZNF174 on tumor stemness markers. The ZNF174 knockdown plasmid was constructed via restriction enzyme digestion and enzyme-linked assembly, while the ZNF174 overexpression plasmid was generated through homologous recombination. Lentiviral infection established stable cell lines with ZNF174 knockdown or overexpression. Tumor stem cell spheroid formation assays were conducted to evaluate stemness maintenance capacity. RNA-seq and quantitative real-time polymerase chain reaction(qPCR) were utilized to detect effects on key stemness gene expression. Results The transcription factor ZNF174 promoted cellular stemness in non-small cell lung cancer(NSCLC). It promoted the expression of key stemness genes: B-cell-specific moloney murine leukemia virus insertion site 1(BMI1), acetaldehyde dehydrogenase 2(ALDH2), SRY-box transcription factor 2(SOX2), recombinant high mobility group AT hook protein 2(HMGA2), and snail family transcriptional repressor 1(Snail1) and enhanced tumor spheroid formation in NSCLC stem cells. Conclusion ZNF174 promotes the expression of tumor stemness genes in NSCLC and may become a novel therapeutic and prognostic target for NSCLC.
[1] Torre L A,Bray F,Siegel R L,et al.Global cancer statistics,2012[J].CA A Cancer J Clin,2015,65(2):87-108.doi:10.3322/caac.21262.
[2] De Francesco E M,Sotgia F,Lisanti M P.Cancer stem cells (CSCs):metabolic strategies for their identification and eradication[J].Biochem J,2018,475(9):1611-34.doi:10.1042/BCJ20170164.
[3] Gopalan V,Islam F,Lam A K.Surface markers for the identification of cancer stem cells[M]//Cancer Stem Cells.New York,NY:Springer New York,2017:17-29.doi:10.1007/978-1-4939-7401-6_2.
[4] Yang L,Shi P,Zhao G,et al.Targeting cancer stem cell pathways for cancer therapy[J].Signal Transduct Target Ther,2020,5(1):8.doi:10.1038/s41392-020-0110-5.
[5] 臧超，戈巧，李超，等.沉默MPZL1调控β-catenin对A549/Tax细胞干性及耐药性的影响[J].安徽医科大学学报，2024,59(1):99-105.doi:10.19405/j.cnki.issn1000-1492.2024.01.016.[5] Zang C,Ge Q,Li C,et al.Effect of silencing MPZL1 on tumor cell stemness and drug resistance of A549/Tax cells via β-catenin signaling[J].Acta Univ Med Anhui,2024,59(1):99-105.doi:10.19405/j.cnki.issn1000-1492.2024.01.016.
[6] 郭欠影，吴正升.可变剪切在恶性肿瘤演进中的研究进展[J].安徽医科大学学报，2025,60(5):778-82.doi:10.19405/j.cnki.issn1000-1492.2025.05.002.[6] Guo Q Y,Wu Z S.Research progress of alternative splicing in the progression of malignant tumors[J].Acta Univ Med Anhui,2025,60(5):778-82.doi:10.19405/j.cnki.issn1000-1492.2025.05.002.
[7] Williams A J,Khachigian L M,Shows T,et al.Isolation and characterization of a novel zinc-finger protein with transcription repressor activity[J].J Biol Chem,1995,270(38):22143-52.doi:10.1074/jbc.270.38.22143.
[8] Stone J R,Maki J L,Blacklow S C,et al.The SCAN domain of ZNF174 is a dimer[J].J Biol Chem,2002,277(7):5448-52.doi:10.1074/jbc.M109815200.
[9] Kapoor-Narula U,Lenka N.Cancer stem cells and tumor heterogeneity:deciphering the role in tumor progression and metastasis[J].Cytokine,2022,157:155968.doi:10.1016/j.cyto.2022.155968.
[10] 张文静，赵可旭，张可越，等.肿瘤干细胞生物学特性及其干性维持机制的研究进展[J].生物工程学报，2024,40(2):391-418.doi:10.13345/j.cjb.230584.[10] Zhang W J,Zhao K X,Zhang K Y,et al.Advances in the biological characteristics and stem maintenance mechanisms of tumor stem cells[J].Chin J Biotechnol,2024,40(2):391-418.doi:10.13345/j.cjb.230584.
[11] Ruan D Y,Wu H X,Meng Q,et al.Development of antibody-drug conjugates in cancer:overview and prospects[J].Cancer Commun (Lond),2024,44(1):3-22.doi:10.1002/cac2.12517.
[12] Xu J,Li L,Shi P,et al.The crucial roles of bmi-1 in cancer:implications in pathogenesis,metastasis,drug resistance,and targeted therapies[J].Int J Mol Sci,2022,23(15):8231.doi:10.3390/ijms23158231.
[13] Zhang H,Fu L.The role of ALDH2 in tumorigenesis and tumor progression:targeting ALDH2 as a potential cancer treatment[J].Acta Pharm Sin B,2021,11(6):1400-11.doi:10.1016/j.apsb.2021.02.008.
[14] Zhu Y,Huang S,Chen S,et al.SOX2 promotes chemoresistance,cancer stem cells properties,and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer[J].Cell Death Dis,2021,12(5):449.doi:10.1038/s41419-021-03733-5.
[15] Mansoori B,Mohammadi A,Ditzel H J,et al.HMGA2 as a critical regulator in cancer development[J].Genes,2021,12(2):269.doi:10.3390/genes12020269.
[16] Tang X,Sui X,Weng L,et al.SNAIL1:linking tumor metastasis to immune evasion[J].Front Immunol,2021,12:724200.doi:10.3389/fimmu.2021.724200.
基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.12.014
中图分类号:R734.2
引用信息:
[1]冯学溢,戴倩.转录因子ZNF174对非小细胞肺癌肿瘤干性的影响[J].安徽医科大学学报,2025,60(12):2308-2315.DOI:10.19405/j.cnki.issn1000-1492.2025.12.014.
基金信息:
国家自然科学基金项目(编号：82103299)~~
2025-12-03
2025-12-03
2025-12-03