The role of miR-4469 as a tumor suppressor regulating inflammatory cell infiltration in colorectal cancer

Background: MicroRNA (miRNA) regulates gene expression posttranscriptionally, and some of them function in tumor suppression and can be used in drug development. As a result, identifying and screening miRNAs that suppress tumors would be a significant addition to tumor treatment. Methods: In this study, we analyzed the miRNA expression profile of colorectal cancer (CRC), constructed a negative regulatory network of the miRNA-target genes, and identified miR-4469 as one of the key tumor suppressors miRNAs. We analyzed the expression and survival of miR-4469 in pan-cancer, experimentally verified the expression level of miR-4469 in CRC cells and the effect on CRC cell proliferation and migration. We screened miR-4469 target genes for enrichment analysis and immune cell infiltration analysis and validated target gene expression to clarify the regulatory mechanisms involved in miR-4469. Results: miR-4469 was more highly expressed in normal colorectum tissues compared to CRC tissues and correlated with survival time in patients with multiple cancers. It was shown that miR-4469 was highly expressed in normal colon cells and miR-4469 expression could inhibit the proliferation and migration of CRC cells. In addition, studies on the mechanism showed that miR-4469 function is mainly related to the regulation of inflammatory cell infiltration, and the key target genes of miR-4469 in this process are SLC2A3, FGR, PLEKHO2, and MYO1F. Conclusion: miR-4469 is a tumor suppressor in CRC, and its regulatory mechanism mainly affects the infiltration of inflammatory cells in the cancer tissue. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.