SE-HOXC13-AS对胰腺癌生物学行为的影响及其临床意义  

Effect of SE-HOXC13-AS on biological behavior of pancreatic cancer and its clinical significance

作　　者：刘天祥[1] 刘露 彭灵智 祝成楼 LIU Tian-xiang;LIU Lu;PENG Ling-zhi;ZHU Cheng-lou(Department of Oncology,Gansu Provincial People’s Hospital,Lanzhou 730000,China;the First Clinical Medical College of Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;the First Clinical Medical College,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]甘肃省人民医院肿瘤外科,兰州730000 [2]甘肃中医药大学第一临床医学院,兰州730000 [3]兰州大学第一临床医学院,兰州730000

出　　处：《临床与实验病理学杂志》2022年第6期669-674,680,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：甘肃省卫生行业科研计划(GSWSKY-2019-04)。

摘　　要：目的探讨超级增强子(super enhancers,SE)-HOXC13-AS对胰腺癌生物学行为的影响及临床意义。方法采用qRT-PCR法检测HOXC13-AS在胰腺癌组织和细胞中的表达,分析HOXC13-AS表达与胰腺癌临床病理特征的关系。选择siRNA转染HOXC13-AS表达量最高的PANC-1细胞,应用CCK-8法、细胞周期实验、划痕实验、Transwell实验及细胞凋亡实验检测敲低HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。应用生物数据库分析和JQ1抑制剂验证SE与HOXC13-AS之间调控关系,并通过CCK-8法、划痕实验、Transwell实验及细胞凋亡实验检测抑制SE-HOXC13-AS对胰腺癌细胞增殖、迁移、侵袭及凋亡的影响。结果胰腺癌组织中HOXC13-AS平均表达量(4.40±6.21)显著高于癌旁组织(1.01±0.02,P<0.05),HOXC13-AS表达与胰腺癌分化程度和临床分期密切相关。与正常胰腺导管上皮细胞(0.93±0.11)相比,胰腺癌细胞株BXPC-3(2.55±0.19)、SW1990(5.49±0.92)、CF-PAC1(12.27±0.60)及PANC-1(70.39±6.40)中HOXC13-AS的表达升高(P<0.05)。敲低PANC-1细胞中HOXC13-AS表达可明显抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。抑制PANC-1细胞中SE可显著下调HOXC13-AS的表达(0.65±0.02 vs 0.41±0.02,P<0.05),并可能进一步抑制胰腺癌细胞增殖、迁移和侵袭能力,促进细胞凋亡。结论HOXC13-AS在胰腺癌中高表达,敲低HOXC13-AS可抑制胰腺癌的进展。SE调控HOXC13-AS的表达,并可能进一步影响胰腺癌的生物学行为。Purpose To investigate the effect of super enhancers(SE)-HOXC13-AS on the biological behavior of pancreatic adenocarcinoma(PDAC)and its clinical significance.Methods qRT-PCR was used to detect the expression of HOXC13-AS in PDAC tissues and cells,and the relationship between HOXC13-AS expression and clinicopathological features of PDAC patients was explored.siRNA was selected to transfect PANC-1 cell with the highest expression of HOXC13-AS,and CCK8 assay,cell cycle assay,scratch assay,transwell assay,and cell apoptosis assay were applied to detect the effects of knocking-down HOXC13-AS on the proliferation,migration,invasion and apoptosis of PDAC cells,respectively.Biological database analysis and JQ1 inhibitor were used to verify the regulatory relationship between SE and HOXC13-AS,and CCK8 assay,scratch assay,transwell assay and cell apoptosis assay were used to detect the inhibitory effects of SE-HOXC13-AS on proliferation,migration,invasion and apoptosis of PDAC cells.Results The average expression of HOXC13-AS in PDAC tissues(4.40±6.21)was significantly higher than that in adjacent normal tissues(1.01±0.02,P<0.05),HOXC13-AS expression was closely correlated with the degree of differentiation and clinical stage.Compared with pancreatic ductal epithelial cells(0.93±0.11),the expression level of HOXC13-AS was increased in PDAC cell lines BXPC-3(2.55±0.19),SW1990(5.49±0.92),CF-PAC1(12.27±0.60)and PANC-1(70.39±6.40).Knocking-down HOXC13-AS expression in PANC-1 cell significantly inhibited the proliferation,migration and invasion,and promoted apoptosis of PDAC cells.Inhibition of SE in PANC-1 cell significantly down-regulated the expression of HOXC13-AS(0.65±0.02 vs 0.41±0.02,P<0.05),and it might further inhibit the proliferation,migration and invasion,and promoted the apoptotic behavior of PDAC.Conclusion HOXC13-AS is highly expressed in PDAC and knocking-down HOXC13-AS can inhibit the progression of PDAC.SE regulates the expression of HOXC13-AS and may further influence the biological behavior of PDAC.

关 键 词：胰腺肿瘤 超级增强子 HOXC13-AS 生物学行为 

分 类 号：R735.9[医药卫生—肿瘤]