Exosomal TFF3 promotes colorectal cancer progression via the LINC00941 pathway

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, characterized by high mortality rate, and a significant reduction in patients’ quality of life. Tumor-derived exosomes act as key mediators of interactions between the cells, and transmit oncogenic signals to nearby or distant cells and promote cancer progression. Trefoil factor 3 (TFF3) has vital function in metastasis, tumor growth, and oncogenic transformation in multiple carcinomas. Nevertheless, regulatory function of exosomal TFF3 and molecular mechanistic processes behind its function in CRC progression are not well understood. Methods: The exosomes were characterized using transmission electron microscopy. Protein expression levels were determined by western blotting. Exosome uptake was assessed using PKH-26 fluorescence in immunofluorescence assays. The colony formation and Cell Counting Kit-8 (CCK-8) assays were used to measure cell proliferation, while Transwell and wound healing assays to evaluate cell invasion and migration abilities. LINC00941 expression was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor growth was assessed in vivo assay, and Ki67 expression was examined through immunohistochemistry (IHC) assay. Results: This work revealed TFF3 being overexpressed in CRC-derived exosomes. Exosomal TFF3 substantially increased CRC cell invasion, migration, and proliferation. Mechanistically, exosomal TFF3 upregulated LINC00941 expression, thereby accelerating CRC progression. The exosomal TFF3 enhanced tumor growth as verified through in vivo experimentation. Conclusions: The research herein demonstrates that CRC metastasis and cell proliferation are promoted by exosomal TFF3 via the upregulation of LINC00941. These outcomes offer newer understanding of exosomal TFF3 function in CRC pathogenesis and may inform future therapeutic strategies.