Circ_0001821 Affects Proliferation and the Cell Cycle in Esophageal Squamous Cell Carcinoma by Elevating BTRC-Mediated IKBA Ubiquitination.

Unlabelled: Esophageal squamous cell carcinoma (ESCC) is a fatal human cancer featured with a tendency to metastasis and relapse. Increasing studies have emphasized the critical roles of circular RNAs (circRNA) in ESCC. This study targeted at a novel circRNA and uncovering its function and mechanisms in ESCC. Functional assays were implemented to evaluate proliferation and cell cycle of ESCC cells. Mechanistic analyses were conducted to explore the potential molecular mechanisms in ESCC cells. In vivo assay was also performed. Based on the collected data, circ_0001821 was highly expressed in ESCC cells. Circ_0001821 knockdown retarded ESCC cell proliferation and tumor growth, while promoting G2-M cell cycle arrest. With regard to its mechanism, RUNX3 promoted PVT1 transcription, further upregulating circ_0001821. Moreover, circ_0001821 sponged miR-423-5p to upregulate BTRC, thus promoting IKBA ubiquitination, and circ_0001821 decreased IKBA expression to activate NF-κB signaling pathway. Rescue assays demonstrated that circ_0001821 facilitated ESCC cell proliferation and cell cycle by downregulating IKBA. In summary, RUNX3-induced circ_0001821 switches on NF-κB signaling pathway via diminishing IKBA expression, functionally prompting ESCC cell proliferation and cell cycle.

Implications: This study uncovered a novel molecular pathway in ESCC progression, which might provide potential biomarkers for ESCC diagnosis.