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环状 RNA circ_0008274 通过海绵吸附 miR-154-3p 调控溶质载体家族 7 成员 11 促进甲状腺乳头状癌细胞的恶性进展。

Circular RNA circ_0008274 enhances the malignant progression of papillary thyroid carcinoma via modulating solute carrier family 7 member 11 by sponging miR-154-3p.

机构信息

Department of Endocrinology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.

Department of Rehabilitation Medicine, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.

出版信息

Endocr J. 2021 May 28;68(5):543-552. doi: 10.1507/endocrj.EJ20-0453. Epub 2021 Jan 19.

DOI:10.1507/endocrj.EJ20-0453
PMID:33473055
Abstract

CircRNAs have been implicated in the progression of human cancers, including papillary thyroid carcinoma (PTC). Although circ_0008274 has been demonstrated as a potential oncogenic circRNA in PTC, our understanding of its molecular determinants is limited. The levels of circ_0008274, miR-154-3p and solute carrier family 7 member 11 (SLC7A11) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). SLC7A11 protein level was assessed by western blot. Cell apoptosis, migration, and adhesion capacities were examined by flow cytometry, transwell and cell adhesion assays, respectively. The targeted correlations among circ_0008274, miR-154-3p and SLC7A11 were confirmed by a dual-luciferase reporter assay. Animal studies were performed to observe the role of circ_0008274 in tumor growth in vivo. Our data showed that the high levels of circ_0008274 and SLC7A11 were associated with poor prognosis of PTC patients. The knockdown of circ_0008274 or SLC7A11 enhanced PTC cell apoptosis and repressed cell migration and adhesion in vitro. Circ_0008274 knockdown suppressed tumor growth in vivo. Mechanistically, circ_0008274 modulated SLC7A11 expression by acting as a sponge of miR-154-3p. SLC7A11 was a functional mediator of circ_0008274 in regulating PTC cell apoptosis, migration and adhesion in vitro, and miR-154-3p overexpression repressed PTC progression in vitro by targeting SLC7A11. Our findings identified that the knockdown of circ_0008274 repressed PTC malignant progression at least in part through regulating the miR-154-3p/SLC7A11 axis, providing a promising therapeutic opportunity for PTC treatment.

摘要

环状 RNA 已被牵连到人类癌症的进展中,包括甲状腺乳头状癌 (PTC)。虽然 circ_0008274 已被证明是 PTC 中的一种潜在致癌环状 RNA,但我们对其分子决定因素的理解有限。通过实时定量聚合酶链反应 (qRT-PCR) 测定 circ_0008274、miR-154-3p 和溶质载体家族 7 成员 11 (SLC7A11) mRNA 的水平。通过 Western blot 评估 SLC7A11 蛋白水平。通过流式细胞术、Transwell 和细胞黏附试验分别检测细胞凋亡、迁移和黏附能力。通过双荧光素酶报告基因实验证实 circ_0008274、miR-154-3p 和 SLC7A11 之间的靶向相关性。进行动物研究以观察 circ_0008274 在体内肿瘤生长中的作用。我们的数据表明,circ_0008274 和 SLC7A11 的高水平与 PTC 患者的预后不良相关。circ_0008274 或 SLC7A11 的敲低可增强 PTC 细胞凋亡并抑制体外细胞迁移和黏附。circ_0008274 敲低可抑制体内肿瘤生长。机制上,circ_0008274 通过充当 miR-154-3p 的海绵来调节 SLC7A11 的表达。SLC7A11 是 circ_0008274 调节体外 PTC 细胞凋亡、迁移和黏附的功能介质,miR-154-3p 通过靶向 SLC7A11 可抑制体外 PTC 进展。我们的研究结果表明,circ_0008274 的敲低至少部分通过调节 miR-154-3p/SLC7A11 轴来抑制 PTC 恶性进展,为 PTC 治疗提供了有前途的治疗机会。

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