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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Circular RNAs (circRNAs) are implicated in tumor development, but their roles in gastric cancer (GC) require further elucidation.
• Many circRNAs associated with GC have undetermined functions and molecular mechanisms.
• circRNA RELL1 (circRELL1) has not been previously investigated in the context of GC.

Purpose of the Study:

• To investigate the role and mechanism of circRNA RELL1 in gastric cancer.
• To determine the relationship between circRELL1 expression and GC prognosis, metastasis, and TNM stage.
• To explore circRELL1's potential as a diagnostic biomarker and therapeutic target for GC.

Main Methods:

• Confirmation of the circular structure of circRELL1.
• In vivo and in vitro functional studies to assess circRELL1's impact on GC cell proliferation, invasion, migration, and apoptosis.
• Investigation of the molecular mechanism involving circRELL1, miR-637, EPHB3, and autophagy.
• Analysis of exosomal transmission of circRELL1 and its effect on GC behavior.

Main Results:

• circRELL1 was significantly downregulated in GC tissues and correlated with poor prognosis, increased lymph node metastasis, and advanced TNM stage.
• circRELL1 suppressed GC cell proliferation, invasion, migration, and promoted apoptosis.
• circRELL1 acted as a sponge for miR-637, indirectly upregulating EPHB3 by modulating autophagy activation.
• Exosomal circRELL1 demonstrated suppressive effects on GC progression both in vivo and in vitro.

Conclusions:

• The circRELL1/miR-637/EPHB3 axis, through modulation of autophagy, plays a suppressive role in GC progression.
• circRELL1 functions as a tumor suppressor in GC.
• circRELL1 holds promise as a novel diagnostic circulating biomarker and therapeutic target for gastric cancer.