lncRNA POLG-DT在非小细胞肺癌新辅助化疗耐药患者组织中高表达并促进癌细胞增殖、迁移和侵袭  

lncRNA POLG-DT is highly expressed in the tissues of patients with non-small cell lung cancer resistant to neoadjuvant chemotherapy and promotes the proliferation,migration and invasion of cancer cells

作　　者：吴永晖 吴文杰 傅文凡 江泽勇 戴璐 赵健 殷俊 WU Yonghui;WU Wenjie;FU Wenfan;JIANG Zeyong;DAI Lu;ZHAO Jian;YIN Jun(Department of Thoracic Surgery,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangdong Guangzhou 510000,China)

机构地区：[1]广州医科大学附属肿瘤医院胸外科,广东广州510000

出　　处：《现代肿瘤医学》2023年第16期2983-2988,共6页Journal of Modern Oncology

基　　金：广东省广州市科技局基础研究计划项目(编号:2060206)。

摘　　要：目的:探究lncRNA POLG-DT在非小细胞肺癌新辅助化疗耐药患者组织中的表达量,观察其对A549和NCI-H1299细胞功能的影响。方法:收集7例非小细胞肺癌新辅助化疗患者术后标本,根据临床疗效分为新辅助敏感组和新辅助耐药组;运用转录组测序检测两组患者中mRNA的表达水平,筛选差异表达的lncRNA,在非小细胞肺癌细胞系中验证POLG-DT的表达量;通过转染si-RNA,下调A549和NCI-H1299细胞中POLG-DT的表达水平,通过CCK8实验、集落形成实验检测细胞的增殖能力,通过Transwell迁移实验、划痕实验检测A549和NCI-H1299细胞迁移和侵袭能力。结果:通过对7例患者的转录组测序,发现POLG-DT在新辅助化疗耐药组表达明显升高,差异有统计学意义(P<0.05);相对于正常肺上皮细胞系BEAS2B,POLG-DT在A549和NCI-H1299细胞中的表达量升高,差异有统计学意义(P<0.05)。下调肺癌细胞中POLG-DT的表达,A549和NCI-H1299细胞增殖、迁移和侵袭能力下降。流式细胞实验显示抑制POLG-DT基因表达能使细胞G_(0)/G_(1)期比例显著上调(P<0.01),S期显著下调(P<0.05)。结论:POLG-DT可通过促进非小细胞肺癌细胞增殖、迁移和侵袭,促进肿瘤发展,促使患者对新辅助化疗耐药。Objective:To explore the expression of lncRNA POLG-DT in the tissues of patients with non-small cell lung cancer resistant to neoadjuvant chemotherapy,and observe its influence on A549 and NCI-H1299 cell functions.Methods:Postoperative specimens of 7 patients with non-small cell lung cancer were collected and divided into neoadjuvant sensitive group and neoadjuvant drug resistant group according to clinical efficacy.Transcriptome sequencing was used to detect the expression level of mRNA in two groups of patients,and the differentially expressed lncRNA was screened to verify the expression of POLG-DT in non-small cell lung cancer cell lines.The expression level of POLG-DT in A549 and NCI-H1299 cells was down-regulated by transfection of si-RNA.The proliferation ability of cells was detected by CCK8 experiment and colony formation experiment.The migration and invasion ability of A549 and NCI-H1299 cells were detected by Transwell migration experiment and scratch experiment.Results:By sequencing the transcriptome of 7 patients,it was found that the expression of POLG-DT was significantly increased in the neoadjuvant chemotherapy resistant group,with statistical significance(P<0.05).Compared with the normal lung epithelial cell line BEAS2B,the expression of POLG-DT in A549 and NCI-H1299 cells increased with statistical significance(P<0.05).Down-regulating the expression of POLG-DT in lung cancer cells,the proliferation,migration and invasion ability of A549 and NCI-H1299 cells decreased.Flow cytometry showed that inhibiting the expression of POLG-DT gene could significantly increase the ratio of G_(0)/G_(1) phase(P<0.01),and decrease the ratio of S phase(P<0.05).Conclusion:POLG-DT can promote the proliferation,migration and invasion of non-small cell lung cancer cells,promote tumor development and make patients resistant to neoadjuvant chemotherapy.

关 键 词：长链非编码RNA POLG-DT 新辅助化疗 化疗耐药 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]