Klinhom-On Nathakan, Seubwai Wunchana, Sawanyawisuth Kanlayanee, Lert-Itthiporn Worachart, Waraasawapati Sakda, Detarya Marutpong, Wongkham Sopit
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand.
Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, 40002, Thailand.
Heliyon. 2021 Apr 22;7(4):e06846. doi: 10.1016/j.heliyon.2021.e06846. eCollection 2021 Apr.
Forkhead box M1 (FOXM1) is a transcriptional factor which plays an important role in oncogenesis. Four FOXM1 isoforms, FOXM1a, FOXM1b, FOXM1c and FOXM1d, are known so far. Different FOXM1 isoforms influence progression of cancer in different cancer types. In this study, the FOXM1c isoform and its impact in cholangiocarcinoma (CCA) was identified. FOXM1c was found to be the predominant isoform in patient-CCA tissues and cell lines. Detection of FOXM1c expression in CCA tissues reflected the worse prognosis of the patients, namely the advanced stage and shorter survival. Suppression of FOXM1 expression using siRNA considerably reduced migration and invasion abilities of CCA cell lines. RNA sequencing analysis revealed claudin-1 as a target of FOXM1. FOXM1 exhibited a negative correlation with claudin-1 expression which was demonstrated in patient CCA tissues and cell lines. FOXM1 may be a potential target for therapeutic treatment of the metastatic CCA.
叉头框蛋白M1（FOXM1）是一种转录因子，在肿瘤发生过程中发挥重要作用。目前已知有四种FOXM1亚型，即FOXM1a、FOXM1b、FOXM1c和FOXM1d。不同的FOXM1亚型在不同类型的癌症中对癌症进展产生不同影响。在本研究中，鉴定了FOXM1c亚型及其在胆管癌（CCA）中的作用。研究发现FOXM1c是患者CCA组织和细胞系中的主要亚型。检测CCA组织中FOXM1c的表达反映了患者预后较差，即处于晚期且生存期较短。使用小干扰RNA（siRNA）抑制FOXM1表达可显著降低CCA细胞系的迁移和侵袭能力。RNA测序分析显示，闭合蛋白-1（claudin-1）是FOXM1的一个靶点。在患者CCA组织和细胞系中证实，FOXM1与claudin-1表达呈负相关。FOXM1可能是转移性CCA治疗的一个潜在靶点。
