PATZ1通过激活p53依赖性途径抑制宫颈癌细胞增殖和迁移的机制研究

PATZ1 inhibits cervical cancer cell proliferation and migration via activating p53-dependent pathway

目的探讨PATZ1激活p53依赖性途径抑制宫颈癌细胞增殖和迁移的机制。方法选取2016-12~2018-12在本院治疗的宫颈癌样本20例,采用qRT-PCR分析患者癌组织以及正常宫颈组织中PATZ1 mRNA表达差异。在宫颈癌细胞HeLa、SiHa及Caski中分别转染PATZ1载体(PATZ1组)与空白载体(CTRL组),采用结晶紫和台盼蓝染色法检测细胞集落形成及细胞增殖活力差异。采用细胞划痕实验及侵袭小室分析细胞侵袭和迁移能力。采用qRT-PCR检测两组细胞中EpCam,Rho E和Caldesmon基因表达差异并分析其调节机制。结果 PATZ1在人宫颈癌组织中的表达水平低于邻近正常组织样本,宫颈癌细胞PATZ1表达水平低于正常宫颈细胞系。PATZ1过表达抑制了集落形成、细胞增殖、迁移和侵袭(P<0.05)。与CTRL组细胞在小鼠内产生的肿瘤相比,PATZ1组肿瘤大小、质量和体积明显较小(P<0.05)。此外与CTRL组比较,PATZ1组细胞系中EpCam表达下调,RhoE和Caldesmon表达上调(均P<0.05)。结论 PATZ1通过调节p53靶基因抑制宫颈癌细胞增殖和迁移。

Objective To investigate the mechanism of PATZ1 inhibiting proliferation and migration of cervical cancer cells via the activation of p53-dependent pathway.Methods Twenty samples from cervical cancer patients in Second Affiliated Hospital of Xi’an Medical College from December 2016 to December 2018 were selected,and the PATZ1 mRNA expression in cancer tissues and normal cervical tissues was detected by qRT-PCR.HeLa,SiHa and Caski cell lines were transfected with PATZ1(PATZ1 group)or empty vector(control group),and then the cell colony formation and the cell proliferation were analyzed by crystal violet and trypan blue staining.Cell invasion and migration were analyzed by cell scratch test and invasion chamber.The expression of EpCam,RhoE and Caldesmon in the two groups was detected by qRT-PCR and the regulatory mechanism was also analyzed.Results PATZ1 expression level was lower in human cervical cancer tumor than that in adjacent normal tissue samples,and PATZ1 expression in cervical cancer cells was lower than that in normal cervical cells.The colony formation,the cell proliferation,the migration and invasion were inhibited after transfection with PATZ1(P<0.05).Compared with control group,the tumor size,the tumor weight and the tumor volume were significantly reduced in PATZ1 group(P<0.05).Compared with control group,EpCam was downregulated in PATZ1 group,whereas RhoE and Caldesmon were upregulated(P<0.05).Conclusion PATZ1 could inhibit the proliferation and the migration of cervical cancer cells by regulating p53 target genes.