Background

Circular RNAs (circRNAs) are a crucial class of regulatory RNAs in cancer procession, including papillary thyroid cancer (PTC). Circ-Pumilio 1 (circPUM1) is a novel circRNA with the oncogenic function in ovarian cancer and lung cancer. However, the role of circPUM1 in PTC is undiscovered.

Objective

This study was performed to investigate the biological function and molecular mechanism of circPUM1 in PTC.

Methods

CircPUM1 and microRNA-21-5p (miR-21-5p) levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular viability and metastasis were measured using Cell Counting Kit 8 (CCK-8) and transwell migration/invasion assay. Glycolysis was evaluated by glucose uptake and lactate production. Associated proteins were examined applying with western blot. Dual-luciferase reporter assay and RNA pull-down assay were used to analyze the interaction between circPUM1 or mitogen-activated protein kinase 1 (MAPK1) and miR-21-5p. Moreover, the role of circPUM1 in vivo was explored by xenograft tumor experiment.

Results

Significantly, circPUM1 was upregulated in PTC tissue samples and cells. Cell growth, metastasis and glycolytic process of PTC cells were all inhibited after downregulation of circPUM1. Besides, circPUM1 could sponge miR-21-5p and MAPK1 was a target gene of miR-21-5p. Furthermore, we found that the anti-cancer effect of circPUM1 knockdown on PTC was partly ascribed to MAPK1 downregulation by upregulating miR-21-5p. Silencing circPUM1 also impeded tumorigenesis of PTC in vivo via miR-21-5p/MAPK1 axis.

Conclusion

These findings suggested that circPUM1 knockdown inhibited MAPK1 expression by targeting miR-21-5p, consequently leading to the repressive effect on PTC progression. CircPUM1 might be a promising target to improve the diagnosis and treatment of PTC.

中文翻译：

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circPUM1的敲低通过作为miR-21-5p的海绵增强MAPK1的表达来阻碍甲状腺乳头状癌的细胞生长、转移和糖酵解

背景

环状 RNA (circRNA) 是癌症进程中的一类关键调节 RNA，包括甲状腺乳头状癌 (PTC)。Circ-Pumilio 1 (circPUM1) 是一种新型 circRNA，在卵巢癌和肺癌中具有致癌功能。然而，circPUM1 在 PTC 中的作用尚未发现。

客观的

本研究旨在研究 circPUM1 在 PTC 中的生物学功能和分子机制。

方法

通过定量实时聚合酶链反应 (qRT-PCR) 分析 CircPUM1 和 microRNA-21-5p（miR-21-5p）水平。使用细胞计数试剂盒 8 (CCK-8) 和 transwell 迁移/侵袭试验测量细胞活力和转移。通过葡萄糖摄取和乳酸产生来评估糖酵解。应用蛋白质印迹检查相关蛋白质。双荧光素酶报告基因测定和 RNA 下拉测定用于分析 circPUM1 或丝裂原活化蛋白激酶 1 (MAPK1) 与 miR-21-5p 之间的相互作用。此外，通过异种移植肿瘤实验探索了circPUM1在体内的作用。

结果

值得注意的是，circPUM1 在 PTC 组织样本和细胞中上调。下调circPUM1后，PTC细胞的细胞生长、转移和糖酵解过程均受到抑制。此外，circPUM1 可以海绵 miR-21-5p，MAPK1 是 miR-21-5p 的靶基因。此外，我们发现 circPUM1 敲低对 PTC 的抗癌作用部分归因于通过上调 miR-21-5p 下调 MAPK1。沉默 circPUM1 还通过 miR-21-5p/MAPK1 轴在体内阻碍了 PTC 的肿瘤发生。

结论

这些发现表明，circPUM1 敲低通过靶向 miR-21-5p 抑制 MAPK1 表达，从而导致对 PTC 进展的抑制作用。CircPUM1 可能是改善 PTC 诊断和治疗的有希望的目标。