环状 RNA DOCK1 通过下调 microRNA-124 诱导人甲状腺癌细胞系的生长。

Circular RNA DOCK1 downregulates microRNA-124 to induce the growth of human thyroid cancer cell lines.

机构信息

Department of Ultrasound, Shengli Oilfield Central Hospital, Dongying, Shandong, China.

Department of Nuclear Medicine, Shengli Oilfield Central Hospital, Dongying, Shandong, China.

出版信息

Biofactors. 2020 Jul;46(4):591-599. doi: 10.1002/biof.1662. Epub 2020 Jun 25.

DOI:10.1002/biof.1662

PMID:32584497

Abstract

BACKGROUND

Both circular RNA DOCK1 (circDOCK1) and microRNA-124 (miR-124) are implicated in carcinogenesis, but functional association between these two molecules remains uncharacterized. Here, we aimed to ascertain the role of circDOCK1-miR-124 node in thyroid cancer cells.

METHODS

circDOCK1 in thyroid cancer specimens from 25 patients was quantified by qRT-PCR. FTC-133 and TPC-1 cells were enforced to overproduce circDOCK1 and miR-124 which were confirmed by qRT-PCR. The alteration in viability, migration and invasion was monitored. Cellular lysis was subjected to Western blot for detecting cyclin D1, p53, matrix metallopeptidase 9 (MMP-9), and vimentin. The phosphorylation of JAK1, STAT3, and AMPK was determined by Western blot.

RESULTS

Results from qRT-PCR showed circDOCK1 was enriched in thyroid carcinoma tissues. circDOCK1 fortified the viability of FTC-133 and TPC-1 cells, as well as their activities to migrate and invade. circDOCK1 increased cyclin D1 and decreased p53, and meanwhile induced the accumulation of MMP-9 and vimentin. miR-124 conferred a reverse effect on the abovementioned alteration. Besides, miR-124 blockaded the phosphorylation of JAK1, STAT3, and AMPK which was induced by circDOCK1.

CONCLUSION

circDOCK1 contributed to thyroid carcinogenesis through inhibition of miR-124 in thyroid cancer cells with dampening signaling transduction of JAK/STAT/AMPK in virtue of miR-124 downregulation.

摘要

背景

环状 RNA DOCK1（circDOCK1）和 microRNA-124（miR-124）都与癌症的发生有关，但这两种分子之间的功能关联尚不清楚。在这里，我们旨在确定 circDOCK1-miR-124 节点在甲状腺癌细胞中的作用。

方法

通过 qRT-PCR 定量检测 25 例甲状腺癌患者的 circDOCK1。通过 qRT-PCR 证实 FTC-133 和 TPC-1 细胞过表达 circDOCK1 和 miR-124。监测细胞活力、迁移和侵袭的变化。对细胞裂解物进行 Western blot 检测，以检测细胞周期蛋白 D1、p53、基质金属蛋白酶 9（MMP-9）和波形蛋白。通过 Western blot 测定 JAK1、STAT3 和 AMPK 的磷酸化。

结果

qRT-PCR 结果显示 circDOCK1 在甲状腺癌组织中丰富。circDOCK1 增强了 FTC-133 和 TPC-1 细胞的活力以及它们迁移和侵袭的能力。circDOCK1 增加了细胞周期蛋白 D1 并降低了 p53，同时诱导了 MMP-9 和波形蛋白的积累。miR-124 对上述变化产生了相反的影响。此外，miR-124 阻断了 circDOCK1 诱导的 JAK1、STAT3 和 AMPK 的磷酸化。