PDF(Pubmed)
Abstract：
Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.
摘要：
前列腺癌（PCa）尤其是抗去势的PCa,是一种常见的致命疾病。Anillin（ANLN）是一种肌动蛋白结合蛋白，与各种恶性肿瘤有关，包括PCA。然而,ANLN在PCa中的调控机制尚不清楚。探索ANLN在PCa发展中的作用以及发现新的治疗靶点对于PCa治疗至关重要。在目前的工作中,我们发现,与附近的非癌前列腺组织和正常前列腺上皮细胞相比,ANLN在PCa组织和细胞系中的表达显著升高.ANLN与更高级的T阶段有关，N级,更高的格里森分数，和前列腺特异性抗原（PSA）水平。此外,我们发现ANLN过表达促进PCa细胞增殖,迁移,和体内外侵袭。机械上,我们进行RNA-seq以鉴定ANLN对MAPK信号通路的调节作用。此外，确定ANLN表达和IGF2BP1表达之间的有利关联。过表达IGF2BP1部分逆转了ANLN下调对PCa细胞生长的肿瘤抑制作用。同时,我们发现ANLN可以通过IGF2BP1稳定原癌基因c-Myc并激活MAPK信号通路。这些发现表明ANLN可能是PCa的潜在治疗靶标。
