Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer

Background: The current study probed into how tumor cell-derived exosomes (Exos) mediated hsa_circ_0001739/lncRNA AC159540.1 to manipulate microRNA (miR)-218-5p/FTO-N6-methyladenosine (m6A)/MYC signal axis in liver metastasis in colorectal cancer (CRC).

Methods: hsa_circ_0001739 and lncRNA AC159540.1 were identified as the upstream regulator of miR-218-5p using ENCORI and LncBase databases. Expression patterns of miR-218-5p, hsa_circ_0001739, lncRNA AC159540.1, FTO, and MYC were detected, accompanied by loss-and-gain-of function assays to examine their effects on CRC cell biological functions. SW480 cells-derived Exos were purified, followed by in vitro studies to uncover the effect of hsa_circ_0001739/lncRNA AC159540.

Results: miR-218-5p was downregulated while hsa_circ_0001739/lncRNA AC159540.1 was upregulated in CRC tissues and cells. Silencing of hsa_circ_0001739/lncRNA AC159540.1 restrained the malignant phenotypes of CRC cells. Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited miR-218-5p to elevate FTO and MYC. The inducing role of Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 in CRC was also validated in vivo.

Conclusion: Conclusively, Exos-mediated circ_0001739/lncRNA AC159540.1 regulatory network is critical for CRC, offering a theoretical basis for CRC treatment.