首页|癌基因NOC2L在上皮-间充质转化过程中抑制前列腺细胞迁移的机制

癌基因NOC2L在上皮-间充质转化过程中抑制前列腺细胞迁移的机制

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目的 探究肿瘤促进基因NOC2L在上皮-间充质转化(EMT)过程中对前列腺癌细胞迁移的影响及分子机制。方法 采用数据库肿瘤基因组图谱(TCGA)、Cioprotal等分析NOC2L差异表达;Transwell、细胞计数试剂盒(CCK-8)、平板克隆等验证分子功能;蛋白质印迹法(Western blot)、聚合酶链反应(PCR)等探究分子机制。两组间比较采用独立样本t检验,多组之间的比较采用单因素方差分析。结果 TCGA:相较于正常前列腺组织,前列腺癌组织中NOC2L基因的表达量相对升高(前列腺癌组织与正常前列腺组织:5。83比5。43,P>0。05);HPA:高级别前列腺癌中NOC2L含量更高(相对染色评分:高级别6。828±0。669比3。909±0。222,t=4。15,P<0。05)。敲低NOC2L抑制细胞迁移、增殖能力,敲低NOC2L后克隆形成数低于对照组(PC3:542。00±35。23比254。00±11。55,t=7。77,P<0。05;RM1:1 406。00±15。34 比 754。00±75。92,t=8。41,P<0。05);CCK-8 培养吸光度低于对照组(PC3:1。657±0。028 比 0。972±0。014,t=21。86,P<0。05;RM1:1。643±0。007比 2。931±0。105,t=12。20,P<0。05);细胞迁移明显低于对照组(PC3:704。00±26。12 比 152。80±6。08,t=20。55,P<0。05;RM 1:704。20±37。56 比 208。40±7。26,t=12。96,P<0。05)。过表达 ZEB1在转录水平抑制 NOC2L 表达(PC3:1。001±0。028 比 0。377±0。018,t=18。62,P<0。05;RM1:1。000±0。012比0。529±0。011,t=28。42,P<0。05),NOC2L在ZEB1表达升高情况下功能逆转抑制细胞迁移,与ZEB1组比较,过表达NOC2L后迁移细胞减少(PC3:899。80±31。17比438。00±12。55,t=13。74,P<0。05;RM1:986。80±65。83 比 466。40±9。67,t=7。82,P<0。05)。结论 NOC2L 促进细胞增殖及迁移,在EMT发生时NOC2L抑制CDH1功能减弱,通过抑制VIM和CDH2发挥抑制细胞迁移作用。
Mechanism of NOC2L protein suppressing the migration of prostate cells in epithelial-mesenchymal transition
Objective To investigate the effect of NOC2L on the migration of prostate cancer cells,and to systematically analyze the molecular mechanism of the contrary effect of NOC2L in the occur-rence of epithelial-mesenchymal transition(EMT).Methods The cancer genome atlas(TCGA),Ciopro-tal and HPA databases were used to analyze the differential expression of NOC2L.Transwell,cell counting kit-8(CCK-8)and plate cloning assays were used to verify the molecular functions.Western blotting and polymerase chain reaction(PCR)were used to explore the molecular mechanism.Results TCGA:Com-pared to normal prostate tissue,the expression of NOC2L gene was relatively higher in prostate cancer tis-sue(prostate cancer tissue vs.normal prostate tissue:5.83 vs.5.43,P>0.05);HPA:NOC2L content was higher in high-grade prostate cancer(relative chromatin staining score:high-grade 6.828±0.669 vs.3.909±0.222,t=4.15,P<0.05).NOC2L knockdown inhibited cell migration and proliferation,and the number of clones formed after NOC2L knockdown was less than that in control group(PC3:542.00±35.23 vs.254.00±11.55,t=7.77,P<0.05;RM1:1406.00±15.34 vs.754.00±75.92,t=8.41,P<0.05);The absorbance of CCK8 culture after NOC2L knockdown was lower than that of control group(PC3:1.657±0.028 vs.0.972±0.014,t=21.86,P<0.05;RM1:1.643±0.007 vs.2.931±0.105,t=12.20,P<0.05).Cell migration was significantly lower after NOC2L knockdown than that of control group(PC3:704.00±26.12 vs.152.80±6.08,t=20.55,P<0.05;RM1:704.20±37.56 vs.208.40±7.26,t=12.96,P<0.05).Overexpression of ZEB1 inhibited the mRNA expression of NOC2L(PC3:1.001±0.028 vs.0.377±0.018,t=18.62,P<0.05;RM1:1.000±0.012 vs.0.529±0.011,t=28.42,P<0.05),and NOC2L reversed function and inhibited cell migration when ZEB1 expression was elevated.Compared with ZEB1 group,after overexpression of NOC2L,the number of migrating cells decreased(PC3:899.80±31.17 vs.438.00±12.55,t=13.74,P<0.05;RM1:986.80±65.83 vs.466.40±9.67,t=7.82,P<0.05).Conclusion NOC2L promotes cell prolifera-tion and migration.During the occurrence of EMT,NOC2L inhibits the function of CDH1 and inhibits cell migration by inhibiting VIM and CDH2.

Prostate cancerEpithelial-mesenchymal transitionZinc finger E-box binding protein 1

丁亚飞、刘景明、刘若阳、黄珍林、杨文龙、顾朝辉、贾占奎、杨锦建

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郑州大学第一附属医院泌尿外科,郑州 450000

前列腺癌 上皮-间充质转化 E盒结合锌指蛋白1

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(8)