FOXM1c is the predominant FOXM1 isoform expressed in cholangiocarcinoma that associated with metastatic potential and poor prognosis of patients
Nathakan Klinhom-on,
Wunchana Seubwai,
Kanlayanee Sawanyawisuth,
Worachart Lert-itthiporn,
Sakda Waraasawapati,
Marutpong Detarya,
Sopit Wongkham
Affiliations
Nathakan Klinhom-on
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand
Wunchana Seubwai
Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand
Kanlayanee Sawanyawisuth
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand
Worachart Lert-itthiporn
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand
Sakda Waraasawapati
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand
Marutpong Detarya
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand
Sopit Wongkham
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 40002, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand; Corresponding author.
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.
