Journal
EXPERIMENTAL CELL RESEARCH
Volume 418, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2022.113266
Keywords
Colorectal cancer; Cancer-associated fibroblasts; Oxaliplatin; Exosome; circN4BP2L2
Categories
Funding
- General Funds of Natural Science Foundation of Hunan Province [2019JJ40480]
Ask authors/readers for more resources
CAF-derived exosomal cricN4BP2L2 promoted CRC cell stemness and oxaliplatin resistance through the EIF4A3/PI3K/AKT/mTOR pathway.
Cancer-associated fibroblasts secreted exosomes (CAFs-exo) are important for tumor carcinogenesis and chemoresistance, but its underlying mechanism in colorectal cancer (CRC) has not yet been clarified. In this study, we investigated the regulatory mechanism of CAFs-exo cricN4BP2L2 on the proliferation, apoptosis, stemness and chemoresistance of LoVo cells. We found that CAFs-exo promoted the oxaliplatin resistance and stemness of LoVo cells, while inhibited the LoVo cell apoptosis. Moreover, knockdown of cricN4BP2L2 in CAFs-exo inhibited the oxaliplatin resistance and stemness characteristics of LoVo cells. Mechanistically, cricN4BP2L2 regulated PI3K/AKT/mTOR axis by binding to EIF4A3. Rescue experiments proved that CAFs-derived exosomal cricN4BP2L2 promoted CRC cells stemness and oxaliplatin resistance by upregulating EIF4A3. Moreover, in vivo experiments showed that depletion of cricN4BP2L2 suppressed CRC tumorigenesis growth. In conclusion, CAFs-exo cricN4BP2L2 promoted the CRC cells stemness and oxaliplatin resistance through EIF4A3/PI3K/AKT/mTOR pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available