Liu Yanwei, Cao Pengwei, Cao Feng, Wang Song, He Yan, Xu Yanyan, Wang Yong
Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei, China.
J Invest Surg. 2022 Feb;35(2):268-277. doi: 10.1080/08941939.2020.1850939. Epub 2021 Mar 23.
Aberrant expression of Anillin (ANLN) has been shown to function in the development of multiple cancers. However, its effects on colorectal carcinoma (CRC) remain unclear. We aimed to explore the role of ANLN in CRC development.
By real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry (IHC), we assessed the expression level of ANLN in CRC tissues and cell lines. The role of ANLN in CRC cell proliferation was evaluated by CCK-8 assays, colony formation assays, EdU assays and cell cycle assays. A mouse tumorigenic model was established to evaluate the in vivo function of ANLN.
We found that ANLN was overexpressed in CRC tissues and cell lines. Highly expressed ANLN correlated with tumor size, tumor number, and stage in patients with CRC. Silencing ANLN in CRC cell lines suppressed proliferation both in vitro and in vivo and induced G0/G1 cell cycle arrest. Downregulation of ANLN led to reduced phosphorylated levels of AKT and ERK. However, total AKT protein showed no change. SP2, a critical transcription factor, was implicated in the upregulation of ANLN.
Our study demonstrated that ANLN regulates CRC cell proliferation via the PI3K/AKT and MAPK pathways, indicating that ANLN may represent a novel and effective target for CRC treatment.
已有研究表明,膜收缩蛋白(ANLN)的异常表达在多种癌症的发生发展中发挥作用。然而,其对结直肠癌(CRC)的影响仍不清楚。我们旨在探讨ANLN在结直肠癌发生发展中的作用。
通过实时定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法和免疫组织化学(IHC),我们评估了ANLN在结直肠癌组织和细胞系中的表达水平。通过CCK-8检测、集落形成检测、EdU检测和细胞周期检测评估ANLN在结直肠癌细胞增殖中的作用。建立小鼠致瘤模型以评估ANLN的体内功能。
我们发现ANLN在结直肠癌组织和细胞系中过表达。在结直肠癌患者中,高表达的ANLN与肿瘤大小、肿瘤数量和分期相关。在结直肠癌细胞系中沉默ANLN可抑制体外和体内的增殖,并诱导G0/G1期细胞周期阻滞。ANLN的下调导致AKT和ERK磷酸化水平降低。然而,总AKT蛋白没有变化。关键转录因子SP2与ANLN的上调有关。
我们的研究表明,ANLN通过PI3K/AKT和MAPK途径调节结直肠癌细胞增殖,这表明ANLN可能是结直肠癌治疗的一个新的有效靶点。