hsa_circ_0001741 promotes esophageal squamous cell carcinoma stemness, invasion and migration by sponging miR-491-5p to upregulate NOTCH3 expression.

ABSTRACT

Circular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). However, the function of circRNAs in ESCC stemness has not been reported. This study aimed to identify novel circRNAs that regulate ESCC stemness and explore their internal mechanisms in ESCC. We found that hsa_circ_0001741 was upregulated in ESCC tissues and was positively related to lymphatic metastasis, higher TNM stage, and poor prognosis. Functionally, hsa_circ_0001741 promoted ESCC cell stemness, invasion, and migration in vitro. Mechanistically, analysis of the relationship between hsa_circ_0001741 and tumor suppressor miR-491-5p revealed that hsa_circ_0001741 functioned as a miR-491-5p sponge. Specifically, hsa_circ_0001741 bound to miR-491-5p to prevent the microRNA from binding to the 3'-UTR of NOTCH3 mRNA and suppressing NOTCH3 expression. Moreover, the ablation of hsa_circ_0001741 significantly inhibited the tumorigenicity in vivo. In conclusion, hsa_circ_0001741 promotes ESCC stemness, invasion, and migration by sponging tumor suppressor miR-491-5p to upregulate NOTCH3 expression. Our findings identify a novel therapeutic target for ESCC patients and the expression level of hsa_circ_0001741 has the potential to serve as a prognostic biomarker for ESCC.