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

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.