Prostate cancer has the highest incidence among men in advanced countries, as well as a high mortality rate. Despite the efforts of numerous researchers to identify a gene-based therapeutic target as an effective treatment of prostate cancer, there is still a need for further research. The cathepsin gene family is known to have a close correlation with various cancer types and is highly expressed across these cancer types. This study aimed at investigating the correlation between the cathepsin A (CTSA) gene and prostate cancer. Our findings indicated a significantly elevated level of CTSA gene expression in the tissues of patients with prostate cancer when compared with normal prostate tissues. Furthermore, the knockdown of the CTSA gene in the representative prostate cancer cell lines PC3 and DU145 led to reduced proliferation and a marked reduction in anchorage-independent colony formation, which was shown to be caused by cell cycle arrest in the S phase. In addition, CTSA gene-knockdown prostate cancer cell lines showed a substantial decrease in migration and invasion, as well as a decrease in the marker genes that promote epithelial mesenchymal transition (EMT). Such phenotypic changes in prostate cancer cell lines through CTSA gene suppression were found to be mainly caused by reduced p38 MAPK protein phosphorylation; i.e. the inactivation of the p38 MAPK cell signaling pathway. Tumorigenesis was also found to be inhibited in CTSA gene-knockdown prostate cancer cell lines when a xenograft assay was carried out using Balb/c nude mice, and the p38 MAPK phosphorylation was inhibited in tumor tissues. Thus, the CTSA gene is presumed to play a key role in human prostate cancer tissues through high-level expression, and the suppression of the CTSA gene leads to the inhibition of prostate cancer cell proliferation, colony formation, and metastasis. The mechanism, by which these effects occur, was demonstrated to be the inactivation of the p38 MAPK signaling pathway.

中文翻译：

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组织蛋白酶a的抑制通过抑制前列腺癌中的p38 MAPK信号通路来抑制生长，迁移和侵袭。

在发达国家，前列腺癌的发病率最高，而且死亡率很高。尽管许多研究人员努力确定基于基因的治疗靶点作为前列腺癌的有效治疗方法，但仍需要进一步的研究。组织蛋白酶基因家族与多种癌症类型密切相关，并且在这些癌症类型中高度表达。这项研究旨在调查组织蛋白酶A（CTSA）基因与前列腺癌之间的相关性。我们的发现表明，与正常前列腺组织相比，前列腺癌患者组织中CTSA基因表达水平显着升高。此外，代表性前列腺癌细胞系PC3和DU145中CTSA基因的敲低导致增殖减少和锚定非依赖性集落形成的明显减少，这被证明是由S期细胞周期停滞引起的。此外，CTSA基因敲低的前列腺癌细胞系显示出迁移和侵袭的显着减少，以及促进上皮间充质转变（EMT）的标记基因的减少。发现通过CTSA基因抑制在前列腺癌细胞系中产生这种表型变化主要是由于p38 MAPK蛋白磷酸化降低所致。即p38 MAPK细胞信号通路的失活。使用Balb / c裸鼠进行异种移植测定后，CTSA基因敲低前列腺癌细胞系中的肿瘤发生也受到抑制，肿瘤组织中p38 MAPK磷酸化受到抑制。因此，推测CTSA基因通过高水平表达在人前列腺癌组织中起关键作用，并且对CTSA基因的抑制导致对前列腺癌细胞增殖，集落形成和转移的抑制。这些作用发生的机制被证明是p38 MAPK信号通路失活的原因。