Exosome-Mediated circRNA Hsa_Circ_0113050 Enhances Colorectal Cancer Cell Malignancy by Interacting with EIF4A3

Abstract

The exosome-mediated circular RNAs (circRNAs) play a crucial role in tumorigenesis. The present study investigated the role of the exosome-mediated circRNA hsa_circ_0113050 in colorectal cancer (CRC) through its interaction with the eukaryotic translation initiation factor 4A3 (EIF4A3). CRC-derived exosomes were isolated and characterized by differential ultracentrifugation, transmission electron microscopy, and nanoparticle tracking analysis. The hsa_circ_0113050 expressions in CRC and exosomes were confirmed through a bioinformatic analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Cell functional and in vivo assays were applied to evaluate the effects of exosomes and hsa_circ_0113050 on CRC cell malignancy. The interaction between EIF4A3 and hsa_circ_0113050 was analyzed by RNA immunoprecipitation, Western blotting, and qRT-PCR assays. CRC-derived exosomes with diameters of 102 and 104 nm enhanced the ability of CRC cells to proliferate, migrate, and invade. hsa_circ_0113050 was highly expressed in CRC tissues and CRC-derived exosomes. Silencing hsa_circ_0113050 in exosomes effectively reversed the exosome-induced CRC cell malignancy. Furthermore, EIF4A3 bound to the linear gene (EIF3I) of hsa_circ_0113050 to enhance the hsa_circ_0113050 expression in the CRC cells. In conclusion, the present study is the first to reveal that exosome-mediated hsa_circ_0113050 enhances CRC cell malignancy by interacting with EIF4A3. Our study findings provide new mechanistic insights into circRNA regulation and highlight a potential therapeutic target for CRC.