FOXK1 plays an oncogenic role in the progression of hilar cholangiocarcinoma

Abstract

Hilar cholangiocarcinoma (HC) has a poor outcome in terms of survival. Forkhead box K1 (FOXK1) dysregulation is critical in solid tumors, which serves a pivotal role in the biological characteristics, such as invasion and migration, but its expression and functions in HC are unclear. The present study investigated the clinical significance and biological functions of FOXK1 in HC. Tumor microarrays and immunohistochemistry were used to evaluate FOXK1 in HC and its expression was modulated to determine its effects on chemoresistance and tumorigenesis. FOXK1 was highly expressed in HC and cell lines, which was associated with tumor invasion, regional lymph node metastasis, tumor recurrence and poor prognosis. Silencing FOXK1 in HC cells inhibited invasion and migration, upregulated E-cadherin, and downregulated vimentin, matrix metallopeptidase 9 and Twist in HC cells. Sensitivity to 5-fluorouracil and cisplatin was increased, and glutathione S-transferase π, multidrug resistance mutation 1 and P-glycoprotein expression levels were downregulated in RBE cells in vitro following FOXK1 knockdown. These results indicated that FOXK1 plays an oncogenic role in HC progression and can serve as a novel therapeutic target for HC.

CircSV2b participates in oxidative stress regulation through miR-5107-5p-Foxk1-Akt1 axis in Parkinson's disease

“…Foxk1 belongs to the Fox family of transcription factors [ 17 ]. Recently, most studies on Foxk1 have focused on tumor-related diseases; there are no reports on its involvement in PD [ 18 , 19 ]. However, studies have found that lncRNAs can regulate the expression of Foxk1 through ceRNAs, thereby participating in disease progression [ 20 , 21 ].…”

circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR‐646/FOXK1 axis

“…It can regulate transcription by binding to the DNA sequence WRTAAAYA and recognizing phosphothreonine peptides with its forkhead‐associated domain 43,44 . FOXK1 is markedly upregulated in multiple cancer types and exerts an oncogenic role 45–47 . Wang et al 48 revealed an upregulated FOXK1 protein level in CRC tissues, and FOXK1 activated Wnt/β‐catenin signaling by promoting DVL nuclear translocation.…”

“…43,44 FOXK1 is markedly upregulated in multiple cancer types and exerts an oncogenic role. [45][46][47] Wang et al 48 27 A recent study showed that FOXK1 could decreased the transcription of glycolytic genes and Hif-1α activation. 28 In fact, our further experiments revealed that FOXK1 could regulate the intracellular ROS production in CRC cells.…”

Identification of a Novel Survival-Related circRNA–miRNA–mRNA Regulatory Network Related to Immune Infiltration in Liver Hepatocellular Carcinoma

“…As one of the cell cycle regulators, CDC25A participates in the radioresistance of various tumor cells ( Ding et al, 2019 )). FOXK1 ( Feng et al, 2021 ) is a member of the FOX transcription factor family. The dysregulation of FOXK1 expression and subcellular localization leads to the uncontrolled development and progression of many tumors.…”