在发达国家，前列腺癌是男性最常见的癌症，大多数死亡是由于晚期和转移性疾病造成的，无法治愈。在这里，我们通过公正的体内筛选发现Mbtps2改变与转移性疾病相关，并证明了它对脂肪酸和胆固醇代谢的调节作用。使用睡莲动物转座子系统随机改变PtenNull小鼠前列腺基因表达。在LNCaP、DU145和PC3细胞系中，通过siRNA敲低MBTPS2，然后进行表型调查。对缺乏MBTPS2的LNCaP细胞进行RNA-Seq，并通过qPCR验证途径。通过Filipin III染色研究胆固醇代谢。在我们的转座子介导的体内筛选中发现Mbtps2与转移性前列腺癌相关。在人前列腺癌细胞系LNCaP、DU145和PC3中沉默MBTPS2表达，可以减少体外的增殖和集落形成生长。在LNCaP细胞中敲低MBTPS2表达会影响胆固醇合成和摄取，同时降低关键的脂肪酸合成调节因子FASN和ACACA的表达。MBTPS2与进展性前列腺癌有关，并可能通过其对脂肪酸和胆固醇代谢的影响发挥机械作用。 ©2023.作者。

Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism.The Sleeping Beauty transposon system was used to randomly alter gene expression in the PtenNull murine prostate. MBTPS2 was knocked down by siRNA in LNCaP, DU145 and PC3 cell lines, which were then phenotypically investigated. RNA-Seq was performed on LNCaP cells lacking MBTPS2, and pathways validated by qPCR. Cholesterol metabolism was investigated by Filipin III staining.Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA.MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.© 2023. The Author(s).