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环状 RNA 100395 抑制甲状腺乳头状癌的恶性转化和糖酵解:涉及 PI3K/AKT/mTOR 信号通路。

Circ_100395 impedes malignancy and glycolysis in papillary thyroid cancer: Involvement of PI3K/AKT/mTOR signaling pathway.

机构信息

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.

出版信息

Immunol Lett. 2022 Jun;246:10-17. doi: 10.1016/j.imlet.2022.04.004. Epub 2022 Apr 18.

Abstract

Circular RNAs (circRNAs) play critical roles in cancer procession, including papillary thyroid cancer (PTC). Despite of published reports regarding the abnormal downregulation of circ_100395 in PTC, the role and regulatory mechanism of which are still undiscovered. Circ_100395 expression was examined via qRT-PCR. Cell growth was detected by the CCK-8 and colony formation, BrdU incorporation and flow cytometry assays. Cell migration and invasion were measured using transwell assays. Aerobic glycolysis was analyzed by the glucose uptake and lactate production. Immunoblotting was performed to evaluate the associated proteins. Decreased circ_100395 expression was shown in PTC tissues and cell lines. Circ_100395 overexpression significantly reduced aerobic glycolysis and the survival, migration and invasion abilities and downregulated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, which were reversed by the PI3K activator 740Y-P. Our data demonstrated that circ_100395 may play an anti-oncogenic role in PTC cells through the inhibition of PI3K/AKT/mTOR signaling pathway.

摘要

环状 RNA(circRNAs)在癌症进程中发挥着关键作用,包括甲状腺乳头状癌(PTC)。尽管已有研究报道 circ_100395 在 PTC 中异常下调,但该分子的作用及其调控机制仍未被发现。通过 qRT-PCR 检测 circ_100395 的表达。通过 CCK-8 检测试剂盒、集落形成实验、BrdU 掺入实验和流式细胞术检测细胞生长。通过 Transwell 实验检测细胞迁移和侵袭。通过葡萄糖摄取和乳酸生成分析有氧糖酵解。通过免疫印迹实验评估相关蛋白。在 PTC 组织和细胞系中观察到 circ_100395 表达下调。circ_100395 的过表达显著降低了有氧糖酵解以及细胞的存活、迁移和侵袭能力,并下调了磷酸肌醇 3-激酶(PI3K)/蛋白激酶 B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路,而该通路可被 PI3K 激活剂 740Y-P 逆转。我们的数据表明,circ_100395 可能通过抑制 PI3K/AKT/mTOR 信号通路在 PTC 细胞中发挥抑癌作用。

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