Objective: Accumulating studies have reported that circular RNAs (circRNAs) can act as novel prognostic biomarkers in multiple malignant tumors. Here, we conducted a study to investigate the potential function and molecular mechanism of action of hsa_circ_0010882 in gastric cancer (GC).
Patients and methods: The expression of hsa_circ_0010882 in the plasma of GC patients and in GC cell lines was verified by qRT-PCR. Its association with overall survival of GC patients was then analyzed by statistical analysis. Gain-of-function and loss-of-function assays were used to investigate the physiological function of hsa_circ_0010882 in GC cells in vitro in the context of proliferation, apoptosis, migration, and invasion. Moreover, the molecular mechanism of action of hsa_circ_0010882 was predicted using online databases and a literature review. A Western blot assay was used to detect the levels of proteins in the PI3K/Akt/mTOR signaling pathway.
Results: We found that hsa_circ_0010882 expression was significantly upregulated in the plasma of GC patients and GC cell lines. Increased expression of hsa_circ_0010882 was significantly correlated with tumor size and histological grade. In addition, GC patients with higher expression of hsa_circ_0010882 had significantly lower overall survival than patients with lower expression of hsa_circ_0010882. Multivariate analysis showed that hsa_circ_0010882 expression could be an independent prognostic factor for overall survival. The proliferation, migration, and invasiveness of GC cell lines were inhibited following hsa_circ_0010882 knock-down, while GC cellular apoptosis increased. Further, overexpression of hsa_circ_0010882 leads to increased proliferation, migration, and invasiveness of GC cell lines. While apoptosis was higher in the GC cell line group with low expressing hsa_circ_0010882 than the control group, no significant difference in apoptosis was detected between the hsa_circ_0010882 overexpressing and the control group. Finally, a mechanistic analysis demonstrated that the hsa_circ_0010882 was positively associated with PI3K/Akt/mTOR signaling pathway.
Conclusions: Hsa_circ_0010882, as an oncogenic molecule, is highly expressed in the plasma of patients with GC and is associated with poor prognosis. It plays an important role in proliferation, migration, and invasive genotypes of GC cell lines via regulation of the PI3K/Akt/mTOR signaling pathway. Additionally, it might be a potential prognostic biomarker for GC patients.