CHSY1 promoted proliferation and suppressed apoptosis in colorectal cancer through regulation of the NFκB and/or caspase‑3/7 signaling pathway

Abstract

Colorectal cancer is a commonly observed malignant cancer. However, the limited therapies for colorectal cancer do not bring much benefit for patients. Chondroitin synthase-1 (CHSY1) is an enzyme responsible for the biosynthesis of chondroitin sulfate and has been implicated in the tumorigenesis of several cancer types; however, there is limited information regarding the role of CHSY1 in colorectal cancer. In the present study, CHSY1 was demonstrated to be highly expressed in colorectal cancer tissues and in cell lines, and the CHSY1 expression level was associated with the 5-year survival rate of patients with colorectal cancer. Following CHSY1 knockdown, the proliferation of colorectal cancer cells was significantly decreased. The number of RKO cells decreased by 50% following CHSY1 knockdown compared with that in the control after culture for 5 days. However, the apoptosis rate of RKO cells increased to 14.15% after CHSY1 knockdown. In addition, the activity of caspase-3/7 was also enhanced. Furthermore, the expression of B-cell lymphoma 2 (Bcl-2) was reduced, whereas the levels of Bcl-2-associated X protein (Bax) and truncated caspase-3/7 were increased following CHSY1 knockdown. Additionally, the phosphorylation level of IκB and the expression of nuclear factor (NF) κB also decreased. In contrast, forced expression of CHSY1 increased the level of Bcl-2, NFκB, and phosphorylated IκB, whereas the level of bax and truncated caspase-3/7 decreased. Therefore, the data of the present study suggest that CHSY1 promoted cell proliferation by regulating NFκB signaling and suppressed cell apoptosis by regulating/caspase-3/7 signaling in colorectal cancer. The present study also suggests that CHSY1 may be a potential target for colorectal cancer therapy.

Adipose-Derived Stem Cells Inhibited the Proliferation of Bladder Tumor Cells by S Phase Arrest and Wnt/β-Catenin Pathway

“…At the initiation of apoptosis, the 116 kDa PARP protein is cut between Asp216-Gly217 into 31 kDa and 85 kDa fragments by caspase-3, making two zinc finger structures that bind to the DNA of PARP separated from the catalytic region at the carboxy terminus, which fails to function normally. As a result, the activity of Ca 2+ /Mg 2+ -dependent endonuclease, which is affected by the negative regulation of PARP, is increased, and DNA between nucleosomes is cleaved, causing apoptosis (Julien and Wells, 2017; Kim and Kim, 2018; Orning et al, 2018; Zeng et al, 2018; Zhu and Li, 2018). Based on these results, we suggest that ADSC-CM induced T24 cell apoptosis via the caspase-3/7 pathway.…”

Transcriptome sequencing analysis of mono‑ADP‑ribosylation in colorectal cancer cells

“…Changes in the expression levels of associated enzymes, such as glycosyltransferases and sulfotransferases, also play an important role during the process of chondroitin sulfate biosynthesis. Additionally, chondroitin sulfate chains promote epithelial-mesenchymal transition (21,22), suggesting that glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate are closely associated with CRC metastasis. In the present study, the association between mono-ADP ribosylation on members of this pathway and the progression of CRC was examined, with the aim of providing a basis for further studying the role of mono-ADP-ribosylation in tumor development and progression.…”

Conditionally immortalised leukaemia initiating cells co-expressing Hoxa9/Meis1 demonstrate microenvironmental adaptation properties ex vivo while maintaining myelomonocytic memory

“…Mutations in Vps45 are associated with congenital neutrophil defect syndrome and impaired neutrophil function 25 . Chsy1 may have a role in the generation and maintenance of neutrophils and macrophages, involved in neurodegenerative processes and proliferation promotion in colorectal cancers 29 , 53 .…”