Circ_0058124通过靶向miR-370-3p激活LMO4表达加重甲状腺乳头状癌进展。
Circ_0058124 Aggravates the Progression of Papillary Thyroid Carcinoma by Activating LMO4 Expression via Targeting miR-370-3p.
作者信息
Liu Lei, Yan Chaohui, Tao Shudong, Wang Hailing
机构信息
Department of Otorhinolaryngology & Head and Neck Surgery, Tianjin Third Central Hospital, Tianjin, People's Republic of China.
Department 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 China.
出版信息
Cancer Manag Res. 2020 Oct 1;12:9459-9470. doi: 10.2147/CMAR.S271778. eCollection 2020.
BACKGROUND
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 () 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 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 , 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 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/ axis, and circ_0058124, functioned as an oncogene in PTC, might be used as a promising biomarker for PTC diagnosis and treatment.
背景
甲状腺癌是内分泌系统中最常见的恶性肿瘤。甲状腺乳头状癌（PTC）在该癌症中占绝大多数病例。近年来，环状RNA（circRNA）在各种癌症中的重要作用已得到认可，本研究旨在探讨circ_0058124在PTC中的作用及其相关作用机制。
材料与方法
采用qRT-PCR检测组织样本（PTC组织或正常组织，n = 20）和细胞系（非癌细胞系Nthy-ori 3-1以及PTC细胞系IHH-4和TPC-1）中circ_0058124、miR-370-3p和仅含LIM结构域蛋白（）的表达。进行功能分析时，使用CCK-8法和集落形成试验研究细胞增殖。采用Transwell试验测定细胞迁移和侵袭能力，并用伤口愈合试验评估细胞迁移情况。通过流式细胞术检测细胞凋亡。进行机制分析时，通过双荧光素酶报告基因试验或RIP试验验证生物信息学分析预测的miR-370-3p与circ_0058124或之间的相互作用。通过建立异种移植模型确定circ_0058124对体内肿瘤生长的影响。
结果
circ_0058124在PTC组织和细胞中表达增强。敲低circ_0058124可抑制PTC细胞的活力、集落形成、迁移和侵袭，并促进细胞凋亡。此外，敲低circ_0058124还可阻断体内肿瘤生长。miR-370-3p是circ_0058124的靶标，circ_0058124通过靶向miR-370-3p调节miR-370-3p的靶标即的表达。拯救实验表明，抑制miR-370-3p可逆转敲低circ_0058124对PTC发展的抑制作用，而过表达可逆转恢复miR-370-3p对PTC发展的影响。
结论
circ_0058124通过介导miR-370-3p/轴促进PTC的发展，在PTC中起癌基因作用的circ_0058124可能作为PTC诊断和治疗的一个有前景的生物标志物。
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