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Pro-tumourigenic effects of DCAF13 on the progression of colorectal cancer
Wenqi Zhang1,2, Rongrong Zhang1, Mengxuan Jia1
1Central Laboratory, Clinical Medicine Research Centre, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China.
Abstract:
Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, with limited effective biomarkers for predicting prognosis and guiding immunotherapy response. The present study aimed to investigate the potential of DDB1- and CUL4-associated factor 13 (DCAF13) as a biomarker for CRC. Bioinformatics analyses were performed using public datasets from The Cancer Genome Atlas and Gene Expression Omnibus; ESTIMATE, CIBERSORT, immune checkpoint, TIDE score and Kaplan-Meier survival analyses were performed to assess the prognostic value and implications of DCAF13 expression in CRC. In silico findings were validated through immunohistochemistry (IHC), in vitro cell-based assays and transcriptomic analysis. Increased DCAF13 expression levels were associated with reduced overall survival in patients with CRC based on the bioinformatics analysis, and this was validated using samples from patients using IHC. Immune profiling demonstrated an increased infiltration of M0 and M1 macrophages, activation of mast cells, neutrophils and CD4+ memory T cells in the DCAF13-high expression group compared with the DCAF13-low expression group. DCAF13 expression was correlated with immune modulators and checkpoint genes. High DCAF13 expression was associated with lower TIDE scores. In vitro assays and transcriptomic analyses confirmed the pro-tumourigenic effects of DCAF13, which demonstrated roles in regulating cell proliferation, migration, clonogenicity, adhesion, metastasis, epithelial-to-mesenchymal transition and homologous recombination in CRC cells. The present study demonstrated that DCAF13 was upregulated in CRC and served a role in tumour progression, thus providing novel insights into the pro-tumourigenic functions of DCAF13 and its potential as a critical regulator in CRC.
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