Department of Nuclear Medicine, The Fifth Affiliated Hospital of Southern Medical University, Conghua District, Guangzhou, China.
The Clinical Specialty 5-Year Undergraduate Course, The First Clinical Medical College of Southern Medical University, Guangzhou, China.
J Gene Med. 2020 Dec;22(12):e3269. doi: 10.1002/jgm.3269. Epub 2020 Sep 18.
Thyroid carcinoma (TC) is the most common malignancy of the endocrine system. Circular RNA (circRNA) is vital in the regulation of tumor progression. Circ_0000144 serves as a novel oncogenic circRNA, and miR-217 is reported to inhibit the malignant phenotypes of cancer cells by targeting AKT3 in TC. The present study aimed to explore the regulatory mechanism of circ_0000144 and miR-217 in the progression of TC.
Circ_0000144 expression in 32 pairs of TC tissues and different TC cell lines (including BCPAP, K1, H7H83, and TPC-1) was detected by employing a quantitative real-time polymerase chain reaction (qRT-PCR). Circ_0000144 small interfering RNA was used to establish loss-of-function models. Cell counting kit-8 (CCK-8), BrdU (5-bromo-2'-deoxyuridine) and transwell assays were utilized to verify the effects of circ_0000144 on TC cell proliferation, migration and invasion, respectively. Bioinformatics, western blotting, a luciferase reporter experiment and qRT-PCR were employed to confirm the relationships among circ_0000144, miR-217 and AKT3.
Circ_0000144 expression was remarkably elevated in TC tissues (p < 0.001) and TC cell lines. The elevation of circ_0000144 expression was markedly linked to tumor size (p = 0.015), TNM stage (p = 0.025) and lymph node metastasis (p = 0.017) of the patients. Functional studies showed that knocking down circ_0000144 repressed the malignancy of TC cells. Furthermore, miR-217 was identified as a downstream target of circ_0000144; inhibition of miR-217 could reverse the effects induced by circ_0000144 knockdown. Moreover, circ_0000144 could regulate AKT3 expression by suppressing miR-217 expression.
Circ_0000144 exerts a cancer-promoting effect on TC cells via the miR-217/AKT3 pathway.
甲状腺癌（TC）是内分泌系统最常见的恶性肿瘤。环状 RNA（circRNA）在肿瘤进展的调控中起着至关重要的作用。Circ_0000144 是一种新型致癌 circRNA，据报道 miR-217 通过靶向 TC 中的 AKT3 抑制癌细胞的恶性表型。本研究旨在探讨 circ_0000144 和 miR-217 在 TC 进展中的调控机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 32 对 TC 组织和不同 TC 细胞系（包括 BCPAP、K1、H7H83 和 TPC-1）中 circ_0000144 的表达。使用 circ_0000144 小干扰 RNA 建立功能丧失模型。细胞计数试剂盒-8（CCK-8）、BrdU（5-溴-2'-脱氧尿苷）和 Transwell 测定分别用于验证 circ_0000144 对 TC 细胞增殖、迁移和侵袭的影响。生物信息学、western blot、荧光素酶报告实验和 qRT-PCR 用于证实 circ_0000144、miR-217 和 AKT3 之间的关系。
TC 组织（p<0.001）和 TC 细胞系中 circ_0000144 的表达显著升高。circ_0000144 表达的升高与患者的肿瘤大小（p=0.015）、TNM 分期（p=0.025）和淋巴结转移（p=0.017）显著相关。功能研究表明，敲低 circ_0000144 抑制了 TC 细胞的恶性表型。此外，miR-217 被鉴定为 circ_0000144 的下游靶标；抑制 miR-217 可以逆转 circ_0000144 敲低引起的效应。此外，circ_0000144 通过抑制 miR-217 的表达来调节 AKT3 的表达。
circ_0000144 通过 miR-217/AKT3 通路对 TC 细胞发挥致癌作用。
