Ke Shuai, Liu Zelin, Wang Qinghua, Zhai Guanzhong, Shao Haoren, Yu Xi, Guo Jia
Department of Urology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan 430060, China.
Cancers (Basel). 2022 Aug 13;14(16):3915. doi: 10.3390/cancers14163915.
Prostate cancer (PCa) is one of the most common cancers and is the second leading cause of mortality in men. Studies exploring novel therapeutic methods are urgently needed. FAM107A, a coding gene located in the short arm of chromosome3, is generally downregulated in PCa and is associated with a poor prognosis. However, the downregulation of FAM107A in PCa and the mechanism of its action remain challenging to determine. This investigation found that downregulation of FAM107A expression in PCa was caused by hypermethylation of CpG islands. Furthermore, DNA methyltransferase 1 (DNMT1) was involved in maintaining hypermethylation. Mechanistically, overexpression of FAM107A inhibits tumor cell proliferation, migration, invasion and promotes apoptosis through the FAK/PI3K/AKT signaling pathway, indicating that FAM107A may be a molecular brake of FAK/PI3K/AKT signaling, thus limiting the active state of the FAK/PI3K/AKT pathway. These findings will contribute to a better understanding of the effect of FAM107A in PCa, and FAM107A may represent a new therapeutic target for PCa.
前列腺癌（PCa）是最常见的癌症之一，是男性第二大死亡原因。迫切需要探索新治疗方法的研究。FAM107A是位于3号染色体短臂上的一个编码基因，在前列腺癌中通常表达下调，且与预后不良有关。然而，FAM107A在前列腺癌中的下调及其作用机制仍难以确定。本研究发现，前列腺癌中FAM107A表达下调是由CpG岛的高甲基化引起的。此外，DNA甲基转移酶1（DNMT1）参与维持高甲基化。从机制上讲，FAM107A的过表达通过FAK/PI3K/AKT信号通路抑制肿瘤细胞增殖、迁移、侵袭并促进凋亡，表明FAM107A可能是FAK/PI3K/AKT信号的分子制动器，从而限制FAK/PI3K/AKT通路的激活状态。这些发现将有助于更好地理解FAM107A在前列腺癌中的作用，并且FAM107A可能代表前列腺癌的一个新治疗靶点。
