Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 4 2025 06 26 481 497 Chunlei Zhang Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China Shiming Yi Department of Hepatobiliary Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China Xiansheng Cao Department of Gastrointestinal Surgery, Hernia and Abdominal Wall Surgery Ⅰ, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China Jiafeng Wang Department of General Surgery, Tai'an City Central Hospital, Tai'an, China 2024 10 22 2024 12 25 MicroRNA (miR)-148a-3p is most frequently upregulated in solid tumors, such as colorectal cancer (CRC). This study aimed to elucidate the role of miR-148a-3p in CRC cell proliferation and immune escape and its potential mechanism. miR-148a-3p and Kruppel-like transcription factor 4 (KLF4) expressions were quantified by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and immune evasion abilities of CRC cells were evaluated with the cell counting kit-8 assay, Transwell, western blot, and enzyme-linked immunosorbent assays. The proliferation or apoptosis of CD8+ and CD4+ T cells after coculture with CRC cells was assessed by flow cytometry. Dual-luciferase reporter gene testing was used to validate the targeting association between KLF4 and miR-148a-3p. A nude mouse subcutaneous graft tumor model was constructed, and CD8+ T cell infiltration was detected by immunohistochemistry and flow cytometry. miR-148a-3p exhibited a high level, while KLF4 was under-expressed in CRC cells; miR-148a-3p negatively regulated the KLF4 level. Overexpression of miR-148a-3p enhanced CRC cell proliferation, migration, invasion, EMT, and immune escape; silencing miR-148a-3p caused the opposite trend; moreover, the said biological functions of CRC cells were weakened with overexpression of KLF4 but enhanced with silencing of KLF4; silencing KLF4 weakened the influences of dampened miR-148a-3p on CRC development. Silencing miR-148a-3p promoted the infiltration of CD8+ T cells and inhibited tumor growth. In summary, miR-148a-3p promotes CRC cell proliferation and immune evasion by regulating the expression of KLF4. This finding can be used for reference when developing a new way of CRC treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4227 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4227/2187