Circular RNA circ-CDYL sponges miR-1180 to elevate yes-associated protein in multiple myeloma

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2020-06, Vol.245 (11), p.925-932
• Main Authors: Chen, Fang, Wang, Xiaohui, Fu, Shuang, Wang, Shaokun, Fu, Yu, Zhang, Jihong, Liu, Zhuogang
• Format: Article
• Language: English
• Subjects: Adult; Animals; Co-Repressor Proteins - genetics; Co-Repressor Proteins - metabolism; Female; Gene Expression Regulation, Neoplastic - genetics; Heterografts; Humans; Hydro-Lyases - genetics; Hydro-Lyases - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Original Research; RNA, Circular - genetics; RNA, Circular - metabolism
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370220918191

The covalently closed circular RNA has recently been proposed as a pivotal player in tumorigenesis. In the current study, we found that circ-CDYL was notably elevated in multiple myeloma tissue and plasma samples and had good diagnostic and prognostic efficacy. Functional assays showed that circ-CDYL enhanced the viability and DNA synthesis of multiple myeloma cells and inhibited apoptosis. Mechanically, cytoplasmic circ-CDYL was co-localized with miR-1180, and circ-CDYL absorbed miR-1180 to upregulate yes-associated protein (YAP), thereby facilitating multiple myeloma progression. Importantly, we further confirmed the existence of this circ-CDYL/miR-1180/YAP regulatory axis in vivo by using the xenograft tumor model. Taken together, our data demonstrate that circ-CDYL is novel promoter of multiple myeloma, and targeting circ-CDYL and its associated network implicates the therapeutic possibility for multiple myeloma patients. Impact statement Multiple myeloma (MM) is an extremely complex and heterogeneous disease, and its pathogenesis is poorly understood. Here, we described an important MM-related circular RNA (circRNA), circ-CDYL. It was remarkably increased in both MM cells and plasma. Depletion of circ-CDYL evidently stunted MM growth. Circ-CDYL could absorb miR-1180 and alleviated the repression of miR-1180 on YAP, leading to increased YAP expression, ultimately triggering MM uncontrolled growth. Therefore, our findings advance the understanding of MM pathogenesis, and also raise the possibility of considering circ-CDYL as a potential therapeutic intervention for MM.