Identification of chondroitin polymerizing factor (CHPF) as tumor promotor in cholangiocarcinoma through regulating cell proliferation, cell apoptosis and cell migration

Abstract

Background: Cholangiocarcinoma (CCA) is a variety of biliary epithelial tumors involving intrahepatic, perihilar and distal bile duct. It is the most common malignant bile duct tumor in the liver and the second most common primary liver cancer, whose molecular mechanism not fully understood. Speci cally, the relationship between CCA and chondroitin polymerizing factor (CHPF) is still not clear. Methods: In this study, detection of clinical specimens was performed to preliminarily study the role of CHPF in cholangiocarcinoma. Cholangiocarcinoma cells with CHPF knockdown were constructed for in vitro study, which was also used in the construction of mice xenograft model for investigating the role of CHPF in the development of cholangiocarcinoma. Results: The results demonstrated that CHPF was signi cantly upregulated in cholangiocarcinoma tissues compared with normal tissues. High expression of CHPF was correlated with more advanced tumor grade. Moreover, knockdown of CHPF signi cantly inhibited cell proliferation, cell migration, promoted cell apoptosis and arrest cell cycle in G2 phase in vitro, as well as suppressed tumor growth in vivo. Conclusions: In conclusion, CHPF was identi ed as a tumor promotor in the development and metastasis of cholangiocarcinoma, which may provide a novel therapeutic target for the targeted therapy against cholangiocarcinoma.

Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation

“…The recent studies found CHPF is significantly up‐regulated in multi‐malignancies, its aberrant expression is related with a poor biological behaviors and predicts a poor prognosis. The high‐expression of CHPF promotes tumor progression and mediates therapeutic resistance (Fan et al 2017; Hou et al 2019b, a; Hou et al 2019b, a; Sun et al 2020; Xu et al 2020; Duan et al 2021; Lin et al 2021). In this study, we found that CHPF is significantly increased in human BRCA tissues (Fig.…”

“…The recent studies reported that CHPF aberrant expression promotes multiple tumor progression and mediates the therapeutic resistance. It is significantly up‐regulated in human melanoma (Sun et al 2020), glioma (Fan et al 2017), gastric cancer (Lin et al 2021), hepatocellular carcinoma (HCC) (Xu et al 2020), cholangiocarcinoma (CCA) (Duan et al 2021), non‐small‐cell lung cancer (NSCLC) (Hou et al 2019b, a; Hou et al 2019b, a) and breast cancer (BRCA) tissues (Li et al 2021a, b, c; Liao et al 2021), the high‐expression of CHPF is closely related with the advanced stage and predicts a poor prognosis. CHPF knockdown can inhibit the proliferation, cell cycle evolution, epithelial‐mesenchymal transition (EMT), migration and invasion in these malignancies.…”

Chemical, Molecular, and Single-nucleus Analysis Reveal Chondroitin Sulfate Proteoglycan Aberrancy in Fibrolamellar Carcinoma

“…CCA is the closest to FLC in terms of CSGALNACT and VCAN upregulation. Intriguingly, CHPF has been reported recently to promote CCA cell growth and invasive potential (56). In addition, CHSY has been reported to suppress apoptosis in colorectal cancer (57) and promote migration in HCC (58).…”

Chemical, molecular, and single cell analysis reveal chondroitin sulfate proteoglycan aberrancy in fibrolamellar carcinoma

“…Cholangiocarcinoma (CCA) is the closest to FLC in terms of CSGALNACT1 and VCAN upregulation. Intriguingly, chondroitin polymerizing factor ( CHPF ) has been reported recently to promote CCA cell growth and invasive potential (44) . Additionally, chondroitin synthase 1 ( CHSY1 ) has been reported to suppress apoptosis in colorectal cancer (45) and promote migration in hepatocellular carcinoma (HCC) (46) .…”