Circular RNAs (circRNAs) hold critical importance due to their notable function in developing Gastric Cancer (GC), which is a malignancy with the third most frequent occurrence worldwide. The aim of this study was to see if circRNA_0044516 would control GC cell proliferation and establish more effective therapeutic strategies.In GC tissues or cells, quantitative Real‑Time Polymerase Chain Reaction (qRT-PCR) was employed for the detection of the expression of circRNA_100349, Insulin-like Growth Factor II (IGF2), and miR-218-5p. CCK-8 assays were employed to gauge the proliferation of cells. A luciferase reporter was employed to establish the relationship of circRNA_100349 or IGF2 with miR-218-5p.CircRNA_100349 was observed to undergo upregulation in GC cell lines along with tissues. GC cell proliferation was prevented by downregulating circRNA_100349. MiR-149 was targeted by CircRNA_100349, and its downregulation increased the amount of miR-218-5p in GC cells. Simultaneously silencing circRNA_100349 decreased IGF2 expression via miR-218-5p, and thus suppressed GC cell proliferation. Furthermore, in nude mice, circRNA_100349 knockdown prevented the tumor development of GC cells.The findings furnished evidence of the critical involvement of circRNA_100349 in GC and that its downregulation impedes GC cell proliferation via the miR-218-5p/IGF2 axis.Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.