Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Department of Medical Oncology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Cell Mol Biol Lett. 2023 Nov 28;28(1):96. doi: 10.1186/s11658-023-00508-y.
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.
PSA 是一种原癌基因，它在胚胎和前列腺癌细胞中特异性和高度表达，但在正常前列腺组织细胞中不表达。前列腺特异性抗原（PSA）的特异性表达被发现与其启动子的条件转录调控有关。CRISPR-dCas9-KRAB 是一种新开发的转录调控系统，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 的表达可能有助于通过单指导 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。在这项研究中，我们检查了不同前列腺癌细胞和正常前列腺上皮细胞中 PSA 启动子的转录活性，确定它确实是一种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，该系统可以在转录水平上抑制前列腺癌细胞中 PSA 基因的表达，从而抑制前列腺癌细胞的恶性生长和迁移，并促进其体外凋亡。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。
