Circular RNA profiling and functional analysis implicate circ-ANKRD36C as a potential prognostic biomarker in gastric cancer.

BACKGROUND: Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide due to its aggressive nature and high metastatic potential. Circular RNAs (circRNAs), characterized by covalently closed loop structures and high molecular stability, have emerged as important regulatory molecules in cancer biology. However, the biological functions and molecular mechanisms of most circRNAs in GC remain largely unexplored. METHODS: We conducted circRNA microarray profiling on three pairs of primary GC tissues and matched adjacent normal tissues to identify differentially expressed circRNAs. The expression of circ-ANKRD36C was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in additional clinical specimens. Functional assays were performed to assess the effects of circ-ANKRD36C knockdown on GC cell proliferation, migration, and invasion. Dual-luciferase reporter assays provided evidence of direct interaction between circ-ANKRD36C and miR-15a-5p. Clinicopathological correlations and survival outcomes were analyzed in 84 paired GC and normal tissue samples. RESULTS: Circ-ANKRD36C was significantly upregulated in GC tissues. Knockdown of circ-ANKRD36C suppressed GC cell proliferation, migration, and invasion in vitro. Dual-luciferase assays supported its direct interaction with miR-15a-5p, potentially influencing oncogenic targets such as BMI1 and CCND1. Clinically, high circ-ANKRD36C expression was associated with shorter overall survival (OS). Multivariate Cox regression analysis suggested its independent prognostic value (hazard ratio [HR] = 2.41; 95% confidence interval [CI] = 1.22–4.77; P = 0.011). CONCLUSION: Circ-ANKRD36C is upregulated in gastric cancer and may serve as a prognostic biomarker. Functional evidence suggests it could act as a candidate regulator, but its mechanistic role requires further validation.