circRNA circ‐CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR‐646

Abstract

Cyclin D1 (CCND1) is a well‐known proliferation promoter that accelerates G1/S transition in cancer. However, the underlying mechanism by which CCND1 is regulated is still largely unknown. In this study, we identified a novel circular RNA (circRNA) derived from CCND1 (circ‐CCND1, hsa_circ_0023303) as a key regulator for CCND1. circ‐CCND1 was found to be markedly up‐regulated in laryngeal squamous cell carcinoma (LSCC) and closely associated with aggressive clinical features and adverse prognosis. Depletion of circ‐CCND1 significantly inhibited LSCC cell proliferation in vitro and retarded tumour growth in vivo . Regarding the mechanism, circ‐CCND1 physically bound to human antigen R (HuR) protein to enhance CCND1 mRNA stability; on the other hand, circ‐CCND1 could act as an effective sponge for miR‐646 to alleviate the repression of miR‐646 on CCND1 mRNA. As a result, circ‐CCND1 post‐transcriptionally elevated CCND1 expression via coordinated avoidance of CCND1 mRNA decay, thereby promoting LSCC tumorigenesis. Taken together, our findings uncover the essential proliferation‐promoting role of circ‐CCND1 through regulation of the stability of CCND1 mRNA in LSCC. Targeting circ‐CCND1 may be a promising treatment for LSCC patients.