Exosomal circRELL1 serves as a miR-637 sponge to modulate gastric cancer progression via regulating autophagy activation

• Published in: Cell death & disease Vol. 13; no. 1; p. 56
• Main Authors: Sang, Huaiming, Zhang, Weifeng, Peng, Lei, Wei, Shuchun, Zhu, Xudong, Huang, Keting, Yang, Jiajia, Chen, Meihong, Dang, Yini, Zhang, Guoxin
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 13.01.2022; Nature Publishing Group UK; Nature Publishing Group
• Subjects: Apoptosis; Autophagy; Autophagy - genetics; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Gastric cancer; Gene Expression Regulation, Neoplastic; Humans; Lymph nodes; Metastases; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular modelling; RNA, Circular - genetics; Stomach Neoplasms - pathology; Therapeutic targets; Tumors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04364-6

Circular RNAs (circRNAs) play a vital role in the occurrence and development of tumors, including gastric cancer (GC). However, there are still many circRNAs related to GC whose functions and molecular mechanisms remain undetermined. Herein, we discover circRNA RELL1, which has not been investigated in GC, and it is markedly downregulated in GC tissues, which is related with poor prognosis, more pronounced lymph node metastasis and poor TNM stage. After confirming the circular structure of circRELL1, we found that circRELL1 could block cell proliferation, invasion, migration, and anti-apoptosis in patients with GC by a series of in vivo and in vitro function-related studies. Further mechanism investigation demonstrated that circRELL1 could sponge miR-637 and indirectly unregulated the expression of EPHB3 via modulating autophagy activation in GC. Additionally, circRELL1 can be transmitted by exosomal communication, and exosomal circRELL1 suppressed the malignant behavior of GC in vivo and in vitro. Taken together, this study elucidates the suppressive roles of circRELL1/miR-637/EPHB3 axis through autophagy activation in GC progression, inspiring for further understanding of the underlying molecular mechanisms of GC and providing a promising novel diagnostic circulating biomarker and therapeutic target in GC.