Abstract
Given the role of chondroitin polymerizing factor (CHPF) in several cancers, we investigated its role in the progression of colorectal cancer (CRC) and its association with NLRP3 inflammasome activation. High expression of CHPF in CRC predicted poor patient prognosis. Using colony formation, EdU staining, wound healing, Transwell invasion, and flow cytometry assays, we revealed that the downregulation of CHPF inhibited the malignant behavior of CRC cells. CHPF promoted NLRP3 inflammasome activation by inducing the MAPK signaling pathway, as evidenced by enhanced expression of Phos-ERK1/2, Phos-MEK1, Phos-MEK2, and NLRP3. Additionally, nuclear factor 1 C-type (NFIC) was revealed as a potential upstream transcription factor of CHPF in the modulation of CRC, and the anti-tumor effects elicited through its knockdown were compromised by CHPF in vitro and in vivo. In summary, we demonstrated that NFIC promoted NLRP3 activation to support CRC development via the CHPF-mediated MAPK signaling.
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This work was supported by Jilin Province for Science and Technology of Traditional Chinese Medicine (Project No: 2023170 and No: 2023171).
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JMW: guarantor of the integrity of the entire study, study concepts, study design, statistical analysis, and manuscript editing. MW: experimental studies, manuscript preparation; YCZ: experimental studies, data analysis, manuscript editing, manuscript review; GHL: study design, definition of intellectual content; YTX: literature research, data acquisition, data analysis.
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The study was approved by the Human Research Ethics Committee of Xiamen Fifth Hospital (approval number: 2019-XMSDWYY-024; approved date: February 21, 2019) and conducted according to the guidelines of the Declaration of Helsinki. All animal experiments performed were approved by the Animal Care and Use Committee of Jiamusi University and conducted in conformance with the Guide for the Care and Use of Laboratory Animals published by the NIH.
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Wu, J., Wang, M., Zhang, Y. et al. Activation of CHPF by transcription factor NFIC promotes NLRP3 activation during the progression of colorectal cancer. Funct Integr Genomics 24, 20 (2024). https://doi.org/10.1007/s10142-024-01299-x
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DOI: https://doi.org/10.1007/s10142-024-01299-x