Esophageal squamous cell carcinoma (ESCC) represents a common malignancy of the digestive system. Circular RNAs (circRNAs) are a distinct class of single-stranded non-coding RNAs that are essential in the progression of various tumors given that they can act as microRNA (miRNA) sponges in a manner similar to that of mRNAs. In this study, circ₀006156 was screened to be highly expressed in ESCC tissues through high-throughput sequencing and quantitative real-time polymerase chain reaction. Subsequent in vitro and in vivo experiments were conducted to validate its biological functions. Furthermore, the regulatory relationships among circ₀006156, miR-202-5p, and TGFBR1 were investigated using RNA antisense purification, miRNA sequencing, RNA immunoprecipitation, fluorescence in situ hybridization, dual-luciferase reporter assay, and bioinformatics analyses. The results showed significant overexpression of circ₀006156 in ESCC tissues, with relatively shorter overall survival observed in patients with high circ₀006156 expression. circ₀006156 was further identified to directly bind to miR-202-5p. miR-202-5p inhibited the proliferation, migration, and invasion of ESCC cells in vitro and partially rescued the effects induced by circ₀006156. Consistent results were reported by subcutaneous xenograft tumor experiments in nude mice. In addition, circ₀006156 was confirmed to act as an endogenous sponge for miR-202-5p, which resulted in a relieved suppression of its target gene TGFβR1. In summary, circ₀006156 can regulate TGFβR1 expression by sponging miR-202-5p, which may further activate the TGFβ/Smad pathway and promote ESCC progression. Collectively, circ₀006156 functions as a novel oncogenic RNA in ESCC and may serve as a potential tumor marker.
Tang et al. (Sun,) studied this question.