PSA is a type of proto-oncogene that is specifically and highly expressed in embryonic and prostate cancer cells, but not expressed in normal prostate tissue cells. The specific expression of prostate-specific antigen (PSA) is found to be related with the conditional transcriptional regulation of its promoter. Clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-KRAB is a newly developed transcriptional regulatory system that inhibits gene expression by interupting the DNA transcription process. Induction of CRISPR-dCas9-KRAB expression through the PSA promoter may help feedback inhibition of cellular PSA gene expression via single guide RNA (sgRNA), thereby monitoring and suppressing the malignant state of tumor cells. In this study, we examined the transcriptional activity of the PSA promoter in different prostate cancer cells and normal prostate epithelial cells and determined that it is indeed a prostate cancer cell-specific promoter.Then we constructed the CRISPR-dCas9-KRAB system driven by the PSA promoter, which can inhibit PSA gene expression in the prostate cancer cells at the transcriptional level, and therefore supress the malignant growth and migration of prostate cancer cells and promote their apoptosis in vitro. This study provides a potentially effective anti-cancer strategy for gene therapy of prostate cancer.

中文翻译：

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由特定PSA启动子驱动的合成CRISPR/dCas9-KRAB系统通过负反馈抑制PSA表达来抑制前列腺癌细胞的恶性生物学行为

PSA是一种原癌基因，在胚胎和前列腺癌细胞中特异性高表达，但在正常前列腺组织细胞中不表达。研究发现前列腺特异性抗原(PSA)的特异性表达与其启动子的条件转录调控有关。成簇规则间隔短回文重复序列 (CRISPR)-dCas9-KRAB 是一种新开发的转录调控系统，可通过中断 DNA 转录过程来抑制基因表达。通过PSA启动子诱导CRISPR-dCas9-KRAB表达可能有助于通过单向导RNA（sgRNA）反馈抑制细胞PSA基因表达，从而监测和抑制肿瘤细胞的恶性状态。在本研究中，我们检测了PSA启动子在不同前列腺癌细胞和正常前列腺上皮细胞中的转录活性，确定其确实是前列腺癌细胞特异性启动子。然后我们构建了由PSA启动子驱动的CRISPR-dCas9-KRAB系统。 PSA启动子能够在转录水平上抑制前列腺癌细胞中PSA基因的表达，从而在体外抑制前列腺癌细胞的恶性生长和迁移，促进其凋亡。这项研究为前列腺癌的基因治疗提供了一种潜在有效的抗癌策略。