去甲基化酶JARID1D在前列腺癌侵袭和转移中的作用与机制

Role and mechanism of demethylase JARID1D in invasion and metastasis of prostate cancer

目的 探索去甲基化酶JARID1D在前列腺癌侵袭和转移中的作用与机制,以期为前列腺癌的转移防治提供新的预测指标及治疗靶点。方法 选择前列腺癌细胞系22RV1和DU145转染慢病毒,以敲低JARID1D的表达,获得细胞系sh-JARID1D,并通过qRT-PCR及Western Blot检测转染后22RV1和DU145细胞中JARID1D的表达情况。通过Transwell实验检测JARID1D低表达后细胞侵袭能力的变化。通过裸鼠尾静脉注射sh-JARID1D细胞系建立体内实验转移模型,观察敲低JARID1D表达后体内肿瘤细胞的转移能力的变化。通过qRT-PCR及Western Blot检测JARID1D对转移相关基因基质金属蛋白酶2(MMP2)表达的影响。结果 Transwell实验显示JARID1D低表达的前列腺癌细胞侵袭能力增强(22RV1细胞系P<0.01,DU145细胞系P<0.001);体内实验显示JARID1D低表达可显著增强肿瘤细胞的体内转移潜能(22RV1转移模型P<0.01,DU145转移模型P<0.01)。进一步实验表明降低JARID1D表达,可提高MMP2的表达。结论 JARID1D低表达可提高前列腺癌细胞中MMP2的表达以增强上皮间质转化(EMT)过程,进而增强前列腺癌的侵袭和转移能力,从而影响前列腺癌的病程发展。

Objective To explore the role and activity mechanisms of demethylase JARID1D in the invasion and metastasis of prostate cancer in order to provide new predictive indicators and therapeutic targets for the metastasis of prostate cancer.Methods The prostate cancer cell lines 22RV1 and DU145 were transfected with lentivirus to knock down the expression of JARID1D.These cell lines were named sh⁃JARID1D.The change in JARID1D expression in sh⁃JARID1D cells was confirmed by qRT⁃PCR and Western Blot.Changes in cell invasion ability after decreasing JARID1D expression were detected by Transwell experiment.An experimental metastasis animal model was established by injecting sh⁃JARID1D cells into the tail vein of nude mice,and changes in tumor cell metastasis ability were evaluated in vivo after knockdown of JARID1D expression.The effect of JARID1D on metastasis⁃related gene matrix metalloproteinase 2(MMP2)was detected by qRT⁃PCR and Western Blot.Results The Transwell experiment showed the increased invasion ability of prostate cancer cells after JARID1D knockdown(22RV1 cell line P<0.01,DU145 cell line P<0.001).We also found that low expression of JARID1D significantly enhanced the metastatic potential of tumor cells in nude mice(22RV1 metastasis model P<0.01,DU145 metastasis model P<0.01).Further experiments demonstrated that reducing the expression of JARID1D promoted the expression of MMP2.Conclusions Knocking down the expression of JARID1D increased the level of MMP2 in prostate cancer cells,promoting epithelial mesenchymal transition,enhancing the invasion and metastasis of prostate cancer,and thus affecting the progression of prostate cancer.