OBJECTIVE: Tumor-derived exosomes have been repeatedly studied as tumor antigens, suppressing T-cell signaling molecules and promoting apoptosis in ovarian cancer (OC). Long non-coding RNAs (lncRNAs) have been recognized as major regulators in tumorigenesis, including OC. For this study, we try to find out the mechanism of exosomes and lncRNA FAL1 in OC.
MATERIALS AND METHODS: After the extraction and identification of exosomes, the internalization of exosomes was observed. Invasion and migration experiments were conducted to investigate the effect of SKOV3 cells-secreted exosomes on OC tumorigenesis and metastasis. Furthermore, the in vivo findings were verified via xenograft tumors in nude mice. FAL1 was knocked out on exosomes. OC cells treated with exosomes were co-cultured with lncRNA FAL1 or/and PTEN to measure cell invasion and migration.
RESULTS: SKOV3-secreted exosomes were absorbed and internalized by OC cells. After exosome treatment, the migration and invasion of OC cells were enhanced, tumors in nude mice were larger and heavier, metastasis was increased, and lncRNA FAL1 expression was increased. When lncRNA FAL1 was knocked out, the promoting effects of SKOV3 cells-secreted exosomes on OC cell metastasis were weakened, along with increased PTEN level and decreased AKT phosphorylation level. In HO-8910PM cells treated with siRNA-FAL1 exosomes and siRNA-PTEN, cell invasion and migration, and AKT phosphorylation were restored.
CONCLUSIONS: SKOV3-secreted exosomes inhibited the PTEN/AKT signaling pathway by transferring lncRNA FAL1, thus inhibiting OC cell metastasis in vitro and in vivo.Free PDF Download
To cite this article
Q. Zhang, T.-Y. Len, S.-X. Zhang, Q.-H. Zhao, L.-H. Yang
Exosomes transferring long non-coding RNA FAL1 to regulate ovarian cancer metastasis through the PTEN/AKT signaling pathway
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 1