Circ_0058124 Aggravates the Progression of Papillary Thyroid Carcinoma by Activating LMO4 Expression via Targeting miR-370-3p

Lei Liu,1 Chaohui Yan,1 Shudong Tao,1 Hailing Wang2 1Department of Otorhinolaryngology & Head and Neck Surgery, Tianjin Third Central Hospital, Tianjin, People’s Republic of China; 2Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaCorrespondence: Hailing WangDepartment of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, North Ring Lake West Road, Heyuan District, Tianjin 300060, People’s Republic of ChinaTel/Fax +86 022– 23340123Email mimohg@163.comBackground: Thyroid cancer is the most common malignant tumor in the endocrine system. Papillary thyroid carcinoma (PTC) accounts for the vast majority of cases in this cancer. Recently, the vital role of circular RNA (circRNA) has been acknowledged in various cancers, and this study aimed to investigate the role of circ_0058124 and related mechanism of its action in PTC.Materials and Methods: The expression of circ_0058124, miR-370-3p and LIM domain only (LMO4) was detected by qRT-PCR in tissue samples (PTC tissues or normal tissues, n=20) and cell lines (non-cancer cell line, Nthy-ori 3– 1, and PTC cell lines, IHH-4 and TPC-1). For functional analysis, cell proliferation was investigated using CCK-8 assay and colony formation assay. Cell migration and invasion were determined using transwell assay, and cell migration was also assessed by wound healing assay. Cell apoptosis was monitored by flow cytometry assay. For mechanism analysis, the interaction between miR-370-3p and circ_0058124 or LMO4 predicted by the bioinformatics analysis was validated by dual-luciferase reporter assay or RIP assay. The effect of circ_0058124 on tumor growth in vivo was identified by establishing the Xenograft model.Results: The expression of circ_0058124 was enhanced in PTC tissues and cells. Circ_0058124 knockdown inhibited viability, colony formation, migration and invasion and promoted apoptosis of PTC cells. Besides, circ_0058124 knockdown also blocked tumor growth in vivo. miR-370-3p was a target of circ_0058124, and circ_0058124 regulated the expression of LMO4, a target of miR-370-3p, by targeting miR-370-3p. Rescue experiments presented that miR-370-3p inhibition reversed the inhibitory effects of circ_0058124 knockdown on PTC development, and LMO4 overexpression reversed the effect of miR-370-3p restoration on PTC development.Conclusion: Circ_0058124 promoted the development of PTC by mediating the miR-370-3p/LMO4 axis, and circ_0058124, functioned as an oncogene in PTC, might be used as a promising biomarker for PTC diagnosis and treatment.Keywords: circ_0058124, miR-370-3p, LMO4, papillary thyroid carcinoma