OncoTargets and Therapy (May 2021)
Circular RNA circWDR27 Promotes Papillary Thyroid Cancer Progression by Regulating miR-215-5p/TRIM44 Axis
Abstract
Weilan Wang,1,* Chengmin Huang,1,* Peng Luo,2 Jiang Yao,1 Jie Li,1 Wenxia Wang,1 Fengqin Liu3 1Department of General Surgery, Changxing People’s Hospital, The Second Affiliated Hospital of Zhejiang University School of Medical Changxing Campus, Changxing, Zhejiang, People’s Republic of China; 2Department of Medical Research, Shanghai Topgen Biomedical Technology Co., Ltd., Shanghai, People’s Republic of China; 3Department of Ultrasound, Changxing People’s Hospital, The Second Affiliated Hospital of Zhejiang University School of Medical Changxing Campus, Changxing, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengqin LiuDepartment of Ultrasound, The Second Affiliated Hospital of Zhejiang University School of Medical Changxing Campus, No. 66 Taihu Middle Road, Changxing, 313100, Zhejiang, People’s Republic of ChinaTel +86-0572-6023641Email [email protected]: This study was to explore the biological roles and underlying mechanism of circRNA WD repeat domain 27 (circWDR27).Methods: The expression of circWDR27, microRNA-215-5p (miR-215-5p) and tripartite motif containing 44 (TRIM44) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were employed to detect cell proliferation. Flow cytometry was used to determine cell apoptosis and cell cycle distribution. Cell migration and invasion abilities were examined by wound healing and transwell assays. The protein levels of matrix metalloproteinase 2 (MMP2), MMP9 and TRIM44 were analyzed by Western blot assay. The relationship between miR-215-5p and circWDR27 or TRIM44 was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assay. Mouse xenograft model was established to examine the role of circWDR27 in vivo.Results: CircWDR27 and TRIM44 were highly expressed while miR-215-5p was lowly expressed in PTC tissues and cells. Knockdown of circWDR27 suppressed cell proliferation and metastasis and induced cell cycle arrest and apoptosis in PTC cells. Moreover, miR-215-5p was a direct target of circWDR27, and its inhibition reversed the suppressive effect of circWDR27 knockdown on PTC cell progression. In addition, miR-215-5p directly targeted TRIM44, and miR-215-5p exerted its anti-cancer role in PTC cells by targeting TRIM44. Furthermore, circWDR27 positively regulated TRIM44 expression by sponging miR-215-5p. Importantly, knockdown of circWDR27 suppressed tumor growth in vivo by upregulating miR-215-5p and downregulating TRIM44.Conclusion: CircWDR27 accelerates PTC progression via regulating miR-215-5p/TRIM44 axis, providing a potential therapeutic target for PTC.Keywords: papillary thyroid cancer, circWDR27, miR-215– 5p, TRIM44
