The miR-181d-5p/SPP1 axis inhibits the migration and invasion of colorectal cancer via the RhoA patyway.

[UNLABELLED] Colorectal cancer (CRC), as the most common malignant tumor, seriously threatens human’s life and safety. Evidence suggests that microRNAs (miRNAs) exhibit an essential role in regulating the occurrence and development of CRC, while the detailed effects and possible mechanisms remain to be further explored. In the present study, a new tumor suppressor function of miR-181d-5p was disclosed in CRC. The expression of miR-181d-5p was obviously decreased in CRC tissues and cell lines. In addition, up-regulation of miR-181d-5p suppressed cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) progress in CRC cells detected by cell transfection, CCK-8, wound healing, transwell migration and western blot assays. Moreover, secreted phosphoprotein 1 (SPP1) was verified as a direct target of miR-181d-5p by binding its 3’-UTR, and confirmed by dual-luciferase reporter assay. Additionally, SPP1 was remarkably increased in CRC tissues and CC cell lines, and was negatively associated with miR-181d-5p expression. Furthermore, over-expression of SPP1 partially restored the inhibitory effects of up-regulated miR-181d-5p on cell viability, migration and EMT progress in CRC cells by modulating RhoA pathway. Finally, up-regulated miR-181d-5p inhibited the tumorigenesis in nude mice by regulating SPP1 mediated with RhoA pathway. To conclude, miR-181d-5p might serve as an effective target for the treatment of patients with CRC.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1038/s41598-026-35040-4.