ADCY6通过上皮-间质转化抑制结直肠癌细胞增殖、迁移和侵袭OACSTPCD
ADCY6 suppresses cell proliferation,migration and invasion via epithelial-mesenchymal transition in colorectal cancer
目的:探究腺苷酸环化酶亚型6(ADCY6)表达量在结直肠癌(CRC)细胞增殖、迁移和侵袭中的作用机制.方法:通过生物信息学数据库分析ADCY6 在各种肿瘤中的表达情况,并分析ADCY6 表达水平与结直肠癌患者不良预后及临床病理特征的关系.使用定量实时逆转录(RT-qPCR)和蛋白质免疫印迹(Western blot)法检测结直肠癌细胞中ADCY6 mRNA和蛋白表达.CCK-8 法检测ADCY6 对结直肠癌细胞增殖的影响,Transwell实验用于检测ADCY6 对细胞迁移和侵袭的影响.将转染ADCY6 过表达载体的结直肠癌细胞皮下注射到BALB/c小鼠中,构建裸鼠移植肿瘤动物模型,计算肿瘤体积和质量,绘制生长曲线.然后在结直肠癌细胞中过表达ADCY6 检测上皮-间充质转化(EMT)关键蛋白的表达以证实ADCY6 通过抑制EMT发挥作用.结果:ADCY6 在多种恶性肿瘤中低表达,ADCY6 mRNA在CRC组织中的表达水平降低,且ADCY6 蛋白在结肠癌中也低表达.ADCY6 的表达与年龄、肿瘤分期和淋巴结转移相关.ADCY6 在FHC细胞中的表达水平高于CRC细胞.过表达ADCY6 可抑制CRC细胞的增殖、迁移和侵袭,且ADCY6 过表达可抑制肿瘤体积和重量.ADCY6 的上调可导致EMT相关的N-钙粘蛋白、波形蛋白和Ki-67 的表达水平降低,同时导致细胞黏附分子的表达水平增升高.结论:ADCY6 的低表达与CRC患者的不良预后有关,且ADCY6 可能通过介导EMT抑制CRC细胞的恶性生物学行为.
Objective:To investigate the mechanism of adenylyl cyclase isoform 6(ADCY6)in suppressing CRC cell prolifera-tion,migration and invasion.Methods:The expression of ADCY6 in various tumors was investigated by bioinformatics database analy-sis.Further analysis of the association among ADCY6 expression levels and poor prognosis and the clinicopathological features of color-ectal cancer patients was performed.The expression of ADCY6 mRNA and protein in CRC cells was measured by conducting quantita-tive real-time reverse-transcription(RT-qPCR)assays and western blotting(WB).A CCK-8 assay was used to detect the effect of AD-CY6 on the proliferation of CRC cells.Transwell was used for cell migration and invasion assays.Xenograft tumours were subcutaneously injection of CRC cells transfected with the ADCY6 overexpression vector into the BALB/c mice,the animal model transplantation tumor in nude mice was constructed,tumor volume and mass was calculated and growth curve were drawed.In addition CRC cells were trans-fected with ADCY6 overexpression vector and the expression of key EMT proteins were tested to confirm ADCY6 play its role by inhibi-ting EMT.Results:The results showed that the expression of ADCY6 was dysregulated in various malignant tumors,and ADCY6 mRNA expression was lower in CRC.Additionally,ADCY6 had lower protein expression in colon cancer tissues.ADCY6 expression was correla-ted with age,tumor stage and lymph node metastasis.ADCY6 expression levels in FHC cells were higher than those in CRC cells.Over-expression of ADCY6 inhibited the proliferation,migration and invasion of CRC cells,and overexpression of ADCY6 hindered tumor growth,includes tumor volume and weight in vitro.Furthermore,upregulation of ADCY6 resulted in a dramatic decrease in the expres-sion of N-cadherin,vimentin and Ki-67 while contributing to a statistically significant increase in the expression of E-cadherin.Conclu-sion:The low expression of ADCY6 is associated with the poor prognosis of CRC patients,and ADCY6 inhibits the malignant biological behaviors of CRC cells by mediating EMT.
周翼;黄世贵;彭洪
川北医学院第二临床医学院·南充市中心医院肛肠外科,四川 南充 637000
临床医学
结直肠癌腺苷酸环化酶亚型6上皮-间充质转化增殖迁移侵袭
Colorectal cancerAdenylyl cyclase isoform 6Epithelial mesenchymal transitioProliferationMigrationInvasion
《川北医学院学报》 2024 (001)
1-7 / 7
四川省医学青年创新科研课题计划(Q22049);四川省南充市市校合作项目(22SXQT0069,22SXQT0070);川北医学院校级课题(CBY22-QNA03)
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