肺腺癌中通过靶向CDT1抑制肿瘤生长及其机制研究  

Targeting CDT1 inhibit tumor growth and its mechanism in lung adenocarcinoma

作　　者：米源[1] 梁宇翔 王聪 李德思 宋春涛 苏洁[1] 张庆财 王雷[2] Mi Yuan;Liang Yuxiang;Wang Cong;Li Desi;Song Chuntao;Su Jie;Zhang Qingcai;Wang Lei(Dept of Emergency,The Fourth Hospital of Hebei Medical University,Shi Jiazhuang 050000;Dept of Thoracic Surgery,The Fourth Hospital of Hebei Medical University,Shi Jiazhuang 050000;Dept of Pharmacy,Hebei Medical University,Shi Jiazhuang 050000;Dept of Medical,The Third Hospital of Hebei Medical University,Hebei Medical University,Shi Jiazhuang 050000;Dept of Sports,Hebei Medical University,Shi Jiazhuang 050000)

机构地区：[1]河北医科大学第四医院急诊科,石家庄050000 [2]河北医科大学第四医院胸二科,石家庄050000 [3]河北医科大学药学院,石家庄050000 [4]河北医科大学第三医院医务处,石家庄050000 [5]河北医科大学体育部,石家庄050000

出　　处：《安徽医科大学学报》2024年第2期260-266,共7页Acta Universitatis Medicinalis Anhui

基　　金：河北省年度医学科学研究计划项目(编号:20221353);河北省重点研发计划项目(编号:22377769D);河北省自然科学基金(编号:H2022206391);河北医科大学第四医院科研创新团队项目(编号:2023B02)。

摘　　要：目的探讨染色质许可和DNA复制因子1(CDT1)在肺腺癌中的价值及作用机制。方法从TCGA数据库中下载肺腺癌组织及正常肺组织基因表达数据及临床信息,通过R语言进行差异分析、GO分析、独立预后分析、与免疫治疗的相关性分析;采集临床样本通过PCR检测CDT1在肺腺癌及正常组织中表达;流式细胞术检测si-CDT1敲低组及si-NC对照组中细胞增殖及周期的变化;Transwell检测各组侵袭能力的变化;Western blot检测各组CDT1、TPX2、p53的表达变化。结果TCGA数据结果显示CDT1为差异基因,GO分析表明CDT1与细胞周期密切相关,在临床样本中验证了CDT1在肺腺癌组织中高表达;CDT1可以作为预测肺腺癌预后的独立因素,并且与肺腺癌免疫治疗的疗效相关;敲低CDT1并与对照组相比,敲低组细胞增殖能力下降,阻滞在G1期,Transwell的结果表明CDT1敲低组侵袭能力降低;敲低CDT1使TPX2下降,p53表达升高,而过表达CDT1得到了相反。结论证实了CDT1在肺腺癌中高表达并与预后差相关,并通过影响TPX2及p53影响肺腺癌的发生发展。Objective To explore the clinical significance and mechanisms of chromatin licensing and DNA replication factor 1(CDT1)in lung adenocarcinoma.Methods The gene expression samples of lung adenocarcinoma tissue and normal lung tissue were downloaded from the TCGA database,and perform differential analysis,GO analysis,independent prognosis analysis,and correlation analysis with immunotherapy using R language.CDT1 expression in lung adenocarcinoma and normal tissues was detected by PCR in clinical samples.The changes of cell proliferation and cycle in si-CDT1 knockdown group and si-NC control group were detected by flow cytometry.The invasive ability of each group was detected by Transwell.The expressions of CDT1,TPX2 and p53 in each group were detected by Western blot.Results The TCGA data analysis revealed CDT1 as a differentially expressed gene.GO analysis indicated that CDT1 was closely associated with the cell cycle.The high expression of CDT1 in lung adenocarcinoma tissues was validated in clinical samples.CDT1 could serve as an independent factor for predicting the prognosis of lung adenocarcinoma and had predictive value for immunotherapy in lung adenocarcinoma.Knockdown of CDT1 resulted in a significant decrease in cell proliferation ability compared to the control group,and cells were noticeably arrested in the G1 phase.Transwell assay results demonstrated a significant reduction in invasive capacity in the CDT1 knockdown group.Knockdown of CDT1 led to a significant decrease in TPX2 expression and a significant increase in p53 expression,while overexpression of CDT1 yielded the opposite effect.Conclusion Results demonstrate the elevated expression of CDT1 in lung adenocarcinoma,its association with prognostic significance,and its impact on lung adenocarcinoma's occurrence and development by influencing TPX2 and p53.

关 键 词：肺腺癌 CDT1 P53 TPX2 肿瘤增殖 

分 类 号：R734.2[医药卫生—肿瘤]