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Cancer Cell International

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Open Access 01-12-2024 | Colorectal Cancer | Research

C6orf15 promotes liver metastasis via WNT/β-catenin signalling in colorectal cancer

Authors: Jiankang Yu, Jian Sun, Jingtong Tang, Jiayu Xu, Guanru Qian, Jianping Zhou

Published in: Cancer Cell International | Issue 1/2024

Abstract

Background

Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel gene that has been reported only in Sjogren’s syndrome and systemic lupus erythematosus patients. We found a close correlation between increased C6orf15 expression and the occurrence of colon cancer. The aim of this study was to explore the potential of C6orf15 as a therapeutic target for colorectal cancer.

Method

RNA-seq differential expression analysis of the TCGA database was performed using the R package ‘limma.’ The correlation between target genes and survival as well as tumour analysis was analysed using GEPIA. Western blot and PCR were used to assess C6orf15 expression in colorectal cancer tissue samples. Immunofluorescence and immunohistochemistry were used to assess C6orf15 subcellular localization and tissue expression. The role of C6orf15 in liver metastasis progression was investigated via a mouse spleen infection liver metastasis model. The association of C6orf15 with signalling pathways was assessed using the GSEA-Hallmark database. Immunohistochemistry (IHC), qPCR and western blotting were performed to assess the expression of related mRNAs or proteins. Biological characteristics were evaluated through cell migration assays, MTT assays, and Seahorse XF96 analysis to monitor fatty acid metabolism.

Results

C6orf15 was significantly associated with liver metastasis and survival in CRC patients as determined by the bioinformatic analysis and further verified by immunohistochemistry (IHC), qPCR and western blot results. The upregulation of C6orf15 expression in CRC cells can promote the nuclear translocation of β-catenin and cause an increase in downstream transcription. This leads to changes in the epithelial–mesenchymal transition (EMT) and alterations in fatty acid metabolism, which together promote liver metastasis of CRC.

Conclusion

Our study identified C6orf15 as a marker of liver metastasis in CRC. C6orf15 can activate the WNT/β-catenin signalling pathway to promote EMT and fatty acid metabolism in CRC.

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Title: C6orf15 promotes liver metastasis via WNT/β-catenin signalling in colorectal cancer
Authors: Jiankang Yu
Jian Sun
Jingtong Tang
Jiayu Xu
Guanru Qian
Jianping Zhou
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Colorectal Cancer
Colorectal Cancer
Metastasis
Colon Cancer
Colon Cancer
Published in: Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-024-03324-2

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