Abstract
Cancer-associated fibroblast (CAF)-derived exosomes play a major role in gastric carcinoma (GC) tumorigenesis. However, the mechanism behind the activity of circular RNAs in CAF-derived exosomes in GC remains unclear. In the present study, we identified differentially expressed circ_0088300 in GC tissues and plasma exosomes. We found that CAFs delivered functional circ_0088300 to GC tumor cells via exosomes and promoted the proliferation, migration and invasion abilities of GC cells. Furthermore, we demonstrated that circ_0088300 packaging into exosomes was driven by KHDRBS3. In addition, we verified that circ_0088300 served as a sponge that directly targeted miR-1305 and promoted GC cell proliferation, migration and invasion. Finally, the JAK/STAT signaling pathway was found to be involved in the circ_0088300/miR-1305 axis, which accelerates GC tumorigenesis. In conclusion, our results indicated a previously unknown regulatory pathway in which exosomal circ_0088300 derived from CAFs acts as a sponge of miR-1305 and promotes GC cell proliferation, migration and invasion; these data identify a potential biomarker and novel therapeutic target for GC in the future.
Highlights
Gastric carcinoma (GC) is one of the most aggressive and common tumors worldwide, in East Asian countries
To identify the Exo-circular RNA (circRNA) involved in gastric carcinoma (GC) tumorigenesis, we first searched the GEO database with “circRNA” and “gastric cancer plasma,” and the results showed that there was only one GSE dataset (GSE93541)
Lots of circular RNAs have become a popular area of research in gastric cancer diagnosis and treatment (Ding et al, 2019; Huang et al, 2019; Zhu et al, 2019; Lu et al, 2020)
Summary
Gastric carcinoma (GC) is one of the most aggressive and common tumors worldwide, in East Asian countries (de Martel et al, 2013). Progress has been made in the early diagnosis and comprehensive therapy of GC, the survival rate of GC patients has been worryingly high in recent years (Mihmanli et al, 2016). The 5-year overall survival rate is 20–25% in patients who suffer from postoperative recurrence and inefficient chemotherapy (Razzak, 2013). It is urgent to explore the deep biological mechanism of GC to enable new diagnoses and therapies for GC patients.
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