SLC30A10 downregulation is associated with cGAS-STING pathway activation in colorectal tubular adenoma.

Based on data-independent acquisition (DIA) proteomics technology, to analyze the proteomic characteristics of colorectal tubular adenoma and explore the expression changes of SLC30A10 and their potential association with the cGAS-STING pathway. A self-controlled design was adopted, collecting colorectal tubular adenoma (TA) and paired normal mucosa (NM) from 15 patients with TA. Differentially expressed proteins were screened by DIA proteomics, followed by GO and KEGG enrichment analyses. Immunohistochemistry was performed to detect the expression of SLC30A10, cGAS, STING, p-IRF3, ISG15, and β-catenin; immunofluorescence double staining was used to observe the co-localization of p-IRF3 and β-catenin; inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine tissue manganese content. DIA analysis showed that SLC30A10 protein expression was significantly downregulated in TA tissues. Functional enrichment analysis indicated abnormalities in signal transduction, metabolic reprogramming, and nitrogen metabolism in TA tissues. IHC results demonstrated that, compared with NM, TA tissues exhibited reduced expression of SLC30A10, while the expression of cGAS, STING, p-IRF3, ISG15, and β-catenin was upregulated. Manganese content in TA tissues was also significantly increased. Immunofluorescence revealed enhanced nuclear signals of p-IRF3 in TA cells, with co-localization of p-IRF3 and β-catenin observed in the nucleus. Downregulation of SLC30A10 in colorectal tubular adenoma is associated with manganese accumulation and alterations in the cGAS-STING pathway, suggesting its potential role in the development and progression of adenoma, a finding with promising research implications.