Regulation of hsa_circ_0112136 by m6A demethylase FTO can enhance the malignancy of gastric cancer via the regulation of the PI3K/AKT/mTOR pathway.

A growing body of research highlights the role that N6-methyladenosine (mA) modification and circular RNAs (circRNAs) play in gastric cancer (GC) cases. However, studies elucidating the function and mechanism of the recently discovered circRNA hsa_circ_0112136 in GC are limited. This study aimed to examine the pathophysiology of GC progression due to fat mass and obesity-associated protein (FTO)-mediated N6-methyladenosine (mA) modification of hsa_circ_0112136. The hsa_circ_0112136 and FTO levels in the GC samples were analyzed using qRT-PCR. The Transwell invasion assay, wound healing assay, and CCK8 assays were employed to assess alterations in GC cell invasiveness, migration, and viability due to the aberrant regulation of hsa_circ_0112136 and FTO. Phosphorylated PI3K, AKT, and mTOR (the key proteins of the PI3K/AKT/mTOR pathway) were detected via western blotting after hsa_circ_0112136 suppression. A tumor transplantation mouse model was constructed to evaluate the suppression of hsa_circ_0112136's function in vivo. The correlation among hsa_circ_0112136 and FTO was identified using the MeRIP assay. Levels of hsa_circ_0112136 and FTO were evidently elevated in GC samples. Suppression of has_circ_0112136 reduced the viability, migration, and invasive ability of GC cells in vitro, as well as delayed tumor growth in vivo via suppression of the activation of the PI3K/AKT/mTOR pathway. FTO decreased hsa_circ_0112136 mA levels and enhanced hsa_circ_0112136 expression. Furthermore, FTO upregulation enhanced GC cell invasion, migration, and survival, which was reversed by hsa_circ_0112136 suppression. Our study proposes that hsa_circ_0112136 functions as a tumor promoter, facilitating the malignant progression of GC through mA modification (suppressed by FTO) and activating the PI3K/AKT/mTOR pathway. This suggests that targeting FTO-mA-hsa_circ_0112136-PI3K/AKT/mTOR may be a novel approach for GC intervention.