[1]王安生,王祖义,郑传明,等.转化生长因子β调节子４对人肺鳞状细胞癌类器官增殖、侵袭和转移的影响[J].新乡医学院学报,2022,39(10):907-911.[doi:10.7683/xxyxyxb.2022.10.002]
　WANG Ansheng,WANG Zuyi,ZHENG Chuanming,et al.Effect of transforming growth factor β regulator 4 on proliferation,invasion and metastasis of human lung squamous cell carcinoma organoids[J].Journal of Xinxiang Medical University,2022,39(10):907-911.[doi:10.7683/xxyxyxb.2022.10.002]
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转化生长因子β调节子４对人肺鳞状细胞癌类器官增殖、侵袭和转移的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年10
页码:
907-911
栏目:
基础研究
出版日期:
2022-10-05

文章信息/Info

Title:
Effect of transforming growth factor β regulator 4 on proliferation,invasion and metastasis of human lung squamous cell carcinoma organoids
作者:
王安生1; 王祖义1; 郑传明2; 陈娜娜1; 李伟3; 洪海宁1; 4; 桑海威1; 王康武1; 李其才1; 陈力维1; 朱浩楠1; 5
（1．蚌埠医学院第一附属医院胸外科，安徽　蚌埠　233004；2.蚌埠医学院第一附属医院急诊外科，安徽　蚌埠　233004；3.蚌埠医学院第一附属医院呼吸病科，安徽　蚌埠　233004；4.蚌埠医学院研究生院，安徽　蚌埠　233030；5.阜阳市人民医院胸外科，安徽　阜阳　236012）
Author(s):
WANG Ansheng1; WANG Zuyi1; ZHENG Chuanming2; CHEN Nana1; LI Wei3; HONG Haining1; 4; SANG Haiwei1; WANG Kangwu1; LI Qicai1; CHEN Liwei1; ZHU Haonan1; 5
(1.Department of Thoracic Surgery,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China;2.Department of Emergency Surgery,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China；3.Department of Respiratory Diseases,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China；4.Graduate School of Bengbu Medical College,Bengbu 233030,China;5.Department of Thoracic Surgery,Fuyang People′s Hospital,Fuyang 236012,China)
关键词:
肺鳞状细胞癌; 增殖; 侵袭; 转移; 转化生长因子β调节子４; 类器官
Keywords:
lung squamous cell carcinoma; proliferation; invasion; metastasis; transforming growth factor β regulator 4; organoids
分类号:
R734.2
DOI:
10.7683/xxyxyxb.2022.10.002
文献标志码:
A
摘要:
目的　探讨转化生长因子β调节子４（TBRG4）在肺癌细胞中的表达及其对人肺鳞状细胞癌类器官增殖、侵袭和转移的影响，并分析可能的分子机制。方法　收集2020年1月至2021年1月蚌埠医学院第一附属医院手术切除的肺鳞状细胞癌患者的癌组织和癌旁组织，采用Western blot法检测癌组织和癌旁组织中TBRG4蛋白的表达。采用胰蛋白酶消化癌组织，分离肿瘤细胞，将分离的肿瘤细胞培养形成人肺鳞状细胞癌类器官。将人肺鳞状细胞癌类器官分为对照组和TBRG4沉默组,对照组类器官转染空载体慢病毒，TBRG4沉默组类器官转染TBRG4沉默慢病毒。采用细胞计数试剂盒-8检测人肺鳞状细胞癌类器官转染24、48、72、96 h时的增殖活力， Transwell法检测人肺鳞状细胞癌类器官的迁移和侵袭能力，Western blot法检测人肺鳞癌类器官中TBRG4、增殖细胞核抗体（PCNA）、磷酸酯酶与张力蛋白同源物（PTEN）、磷酸化磷脂酰肌醇激酶（p-PI3K）、磷酸化蛋白激酶B(p-AKT)蛋白表达。结果　肺鳞状细胞癌组织中TBRG4蛋白相对表达量显著高于癌旁组织（P<0.05）。TBRG4沉默组人肺鳞状细胞癌类器官转染24、48、72、96 h时的增殖活力均显著高于对照组（P<0.05）。TBRG4沉默组穿膜细胞数和迁移细胞数均显著少于对照组（P<0.05）。TBRG4沉默组人肺鳞状细胞癌类器官中TBRG4、PCNA、p-PI3K、p-AKT蛋白的相对表达量均显著低于对照组（P<0.05），PTEN蛋白的相对表达量显著高于对照组（P< 0.05）。结论　TBRG4在肺鳞状细胞癌组织中高表达，其可能是通过PTEN/PI3K/AKT信号通路调节人肺鳞状细胞癌类器官的增殖、侵袭和转移，TBRG4有望成为肺癌治疗的新靶点。
Abstract:
Objective　To investigate the expression of transforming growth factor β regulator 4（TBRG4） in lung cancer cells and its effect on proliferation,invasion and metastasis of human lung squamous cell carcinoma organoids,and to analyze the possible molecular mechanism.Methods　The cancerous tissues and adjacent tissues removed from patients with human lung squamous cell carcinoma admitted at the First Affiliated Hospital of Bengbu Medical College from January 2020 to January 2021 were collected,and the expression of TBRG4 protein in cancerous tissues and adjacent tissues was detected by Western blot.Cancer tissue was digested with trypsin,and the tumor cells were isolated,then the isolated tumor cells were cultured to form human lung squamous cell carcinoma organoids.The human lung squamous cell carcinoma organoids divided into control group and TBRG4 silencing group.The organoids in the control group were transfected with empty vector lentivirus,the organoids in the TBRG4 silencing group were transfected with TBRG4 silencing lentivirus.The proliferation activity of human lung squamous cell carcinoma organoids was detected by cell counting kit-8,the migration and invasion ability of human lung squamous cell carcinoma organoids were detected by Transwell method,and the expressions of TBRG4,proliferating cell nuclear anlibody(PCNA),phosphatase and tensin homolog (PTEN),phosphorylated phosphatidylinositol-3-kinase(p-PI3K),phosphorylated protein kinase B (p-AKT) protein were detected by Western blot.Results　The relative expression of TBRG4 protein in lung squamous cell carcinoma tissues was significantly higher than that in adjacent tissues (P<0.05).The proliferation activity of human lung squamous cell carcinoma organoids in the TBRG4 silencing group was significantly higher than that in the control group at 24,48,72,96 h after transfection.The number of transmembrane cells and the number of cell migration in the TBRG4 silencing group were significantly less than those in the control group (P<0.05).The relative expressions of TBRG4,PCNA,p-PI3K and p-AKT protein in human lung squamous cell carcinoma organoids in the TBRG4 silencing group were significantly lower than those in the control group (P<0.05),the relative expression of PTEN protein was significantly higher than that in the control group(P<0.05).Conclusion　TBRG4 is highly expressed in human lung squamous cell carcinoma，which may regulate the proliferation,invasion and metastasis of human lung squamous cell carcinoma organoids through PTEN/PI3K/AKT signaling pathway.TBRG4 is expected to become a new target for the treatment of lung cancer.

参考文献/References:

［1］　BRAY F,FERLAY J,SOERJOMATARAM I，et al．Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2018,68(6):394-424.
［2］　ZENG H,CHEN W,ZHENG R,et al.Changing cancer survival in China during 2003-15:a pooled analysis of 17 population-based cancer registries［J］.Lancet Glob Health,2018,6(5):e555-e567.
［3］　HANNIGAN B，YE W，MEHROTRA M，et al．Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine needle aspiration specimens［J］．Ann Oncol,2019,1(1):1-9.
［4］　HUCH M,KOO B K.Modeling mouse and human development using organoid cultures［J］.Development,2015,142(18):3113-3125.
［5］　SCHUTGENS F,CLEVERS H.Human organoids:tools for understanding biology and treating diseases［J］.Annu Rev Pathol,2020,24(15):211-234.
［6］　MONTAZER-TORBATI M B,HUE-BEAUVAIS C,DROINEAU S,et al.Epigenetic modifications and chromatin loop organization explain the different expression profiles of the Tbrg4,WAP and Ramp3 genes［J］.Exp Cell Res,2008,314(5):975-987.
［7］　潘有光,傅文凡,莫益俊,等．miR-92b-3p通过靶向RAD21增强非小细胞肺癌对顺铂的化学敏感性 ［J］.实用医学杂志,2020,11(14):1897-1902.
PAN Y G,FU W F,MO Y J,et al.Enhancement of chemosensitivity to cisplatin in non small cell lung cancer through miR-92b-3p by targeting RAD21 ［J］.J Pract Med,2020,11(14):1897-1902.
［8］　郭浩,周淑妮,冉瑞智.吉非替尼联合培美曲塞和顺铂治疗晚期非小细胞肺癌的安全性和有效性［J］.现代肿瘤医学,2019,27(5):796-800．
GUO H,ZHOU S N,RAN R Z.Safety and efficacy of gefitinib combined with pemetrexed and cisplatin in the treatment of advanced non-small cell lung cancer ［J］.J Modern Oncol,2019,27(5):796-800．
［9］　GUO D,WANG B,HAN F,et al.RNA interference therapy for glioblastoma ［J］.Expert Opin Biol Ther,2010,10(6):927-936.
［10］　WIZNEROWICZ M,TRONO D.Harnessing HIV for therapy,basic research and biotechnology ［J］.Trends Biotechnol,2005,23(1):42-47.
［11］　SUI G,SOOHOO C,AFFAR EL B,et al.A DNA vector based RNAi technology to suppress gene expression in mammalian cells ［J］.Proc Natl Acad Sci USA,2002,99(8):5515-5520.
［12］　叶柯,郑晓丽,葛红,等.TBRG4在肺腺癌中的作用及其机制研究［J］.中国癌症杂志,2019,29(4):265-271.
YE K,ZHENG X L,GE H,et al.Study on the role of TBRG4 in lung adenocarcinoma and its mechanism［J］.China Oncol,2019,29(4):265-271.
［13］　张伟.线粒体蛋白TBRG4在乳腺癌中的功能研究［D］.上海：复旦大学,2011.
ZHANG W.Function of the mitochondrial protein TBRG4 in breast cancer［D］.Shanghai：Fudan University,2011.
［14］　廖法学.转化生长因子β调节蛋白4在骨肉瘤增殖、凋亡中的作用及其机制的初步探讨［D］.合肥：安徽医科大学,2019.
LIAO F X.The role of transformative growth factor β regulatory protein 4 in osteosarcoma proliferation and apoptosis and its mechanism are preliminary discussion ［D］.Hefei：Anhui Medical University,2019.
［15］　徐晓恩.以同一病人来源的系列乳腺细胞系研究乳腺癌致病的蛋白质基础［D］.上海：复旦大学,2011.
XU X E.Protein basis for studying breast cancer pathogenesis using a series of breast cell lines of the same patient source［D］.Shanghai：Fudan University,2011.
［16］　DE ASSIS L V,ISOLDI M C.The function,mechanisms,and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma:a review focused on the genes′ molecular mechanisms［J］.Tumour Biol,2014,35(2):889-901.
［17］　PREZ-RAMREZ C,CA N~ADAS-GARRE M,MOLINA M ,et al.PTEN and PI3K/AKT in non-small-cell lung cancer［J］.Pharmacogenomics，2015，16(16):1843-1862.
［18］　柳亮,张志强,吴瑞峰,等.PTEN及FOXC1在非小细胞肺癌组织中的表达及临床意义［J］.现代医药卫生,2020,36(13):1980-1983.
LIU L,ZHANG Z Q,WU R F,et al.Expression and significance of PTEN and FOXC1 in the tissues of non-small cell lung cancer ［J］.J Mod Med Health,2020,36(13):1980-1983.

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更新日期/Last Update: 2022-10-05