Colorectal cancer-derived extracellular vesicles are enriched in miR-1290 and transfer it to parental cells.

Extracellular vesicles (EVs) are a heterogeneous population of membrane-bound particles that mediate intercellular communication through the horizontal transfer of biologically active cargo, including microRNAs (miRNAs). Although numerous miRNAs have been identified in EVs, it remains unclear which miRNAs are selectively enriched and how they contribute to EV-mediated biological effects in recipient cells. Using colorectal cancer (CRC) as a model system, we investigated the selective enrichment of EV-associated miR-1290 and explored its potential biological relevance. EVs were isolated from CRC cell lines and patients' plasma by ultracentrifugation and characterized according to current guidelines. Small RNA sequencing of CRC cells and their EVs revealed selective enrichment of miR-1290 in CRC-derived EVs, which was validated by RT-qPCR. Sequence analysis of miR-1290 revealed the putative AGGG EXOmotif in the canonical sequence and most detected isomiR variants, including the most abundant isomiR, while the GGAG EXOmotif, previously implicated in miRNA sorting into EVs, was present in the most abundant isomiR and several additional isomiR variants. Transfer experiments demonstrated that CRC-derived EVs efficiently deliver miR-1290 to parental cancer cells in an auto-/paracrine manner. CRC-EV uptake modulated the expression of the predicted miR-1290 target genes FGF2 and EPCAM, as assessed by RT-qPCR, ELISA, and flow cytometry; however, the observed effects were not solely attributable to miR-1290, suggesting a contribution of additional EV cargo components. In plasma samples from CRC patients and healthy donors, miR-1290 was detected in both plasma-derived EVs and the EV-depleted plasma fraction, with slightly higher levels observed in CRC patients. Together, these findings show that miR-1290 is selectively enriched in CRC-derived EVs and transferred to recipient cells. The presence of conserved EXOmotifs supports the possible involvement of selective EV-sorting mechanisms, while the biological effects of CRC-derived EVs likely reflect the combined effects of multiple cargo components. Detection of miR-1290 in circulating EVs further highlights its potential as a complementary biomarker candidate in CRC.