Previous studies have identified the dysregulation of various circRNAs in many types of human cancers including thyroid cancer (TC). Circular RNA ZFR (circZFR) serves as an oncogenic circRNA in TC. However, the detailed molecular mechanism of circZFR in TC progression remains to be further explored. CircZFR and miR-16 expressions in TC cells were analyzed through qRT-PCR. Cell viability, invasion, and apoptosis were detected using CCK-8, transwell invasion assay, and flow cytometry analysis, respectively. The relationship between circZFR and miR-16 was explored using luciferase reporter assay, RNA pull-down assay, and qRT-PCR. The relationship between miR-16 and mitogen-activated protein kinase 1 (MAPK1) was explored using luciferase reporter assay and western blot analysis. Results showed that circZFR was upregulated and miR-16 was downregulated in TC cells. CircZFR knockdown inhibited the viability and invasion and induced apoptosis in TC cells. CircZFR inhibited miR-16 expression by sponging miR-16 and miR-16 repressed MAPK1 expression by targeting MAPK1. Moreover, circZFR positively regulated MAPK1 expression in TC cells by serving as a ceRNA of miR-16. Mechanistically, circZFR knockdown-induced inhibition of cell viability and invasion and promotion of apoptosis were overturned after miR-16 downregulation and promotion of MAPK1. Collectively, circZFR knockdown retarded TC progression by sponging miR-16 and modulating MAPK1 expression.

中文翻译：

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circZFR 通过 miR-16/MAPK1 轴调节甲状腺癌进展

先前的研究已经确定了包括甲状腺癌 (TC) 在内的多种人类癌症中各种 circRNA 的失调。环状 RNA ZFR (circZFR) 作为 TC 中的致癌 circRNA。然而，circZFR在TC进展中的详细分子机制仍有待进一步探索。通过qRT-PCR分析TC细胞中CircZFR和miR-16的表达。分别使用 CCK-8、transwell 侵袭试验和流式细胞术分析检测细胞活力、侵袭和凋亡。使用荧光素酶报告基因检测、RNA 下拉检测和 qRT-PCR 探索了 circZFR 和 miR-16 之间的关系。使用荧光素酶报告基因检测和蛋白质印迹分析探索了 miR-16 和丝裂原活化蛋白激酶 1 (MAPK1) 之间的关系。结果表明，TC细胞中circZFR上调，miR-16下调。CircZFR 敲低抑制了 TC 细胞的活力和侵袭并诱导了细胞凋亡。CircZFR 通过海绵 miR-16 抑制 miR-16 表达，而 miR-16 通过靶向 MAPK1 抑制 MAPK1 表达。此外，circZFR 通过作为 miR-16 的 ceRNA 正向调节 TC 细胞中的 MAPK1 表达。从机制上讲，在 miR-16 下调和促进 MAPK1 后，circZFR 敲低诱导的细胞活力抑制和侵袭和促进细胞凋亡被推翻。总的来说，circZFR 敲低通过海绵 miR-16 和调节 MAPK1 表达来延缓 TC 进展。CircZFR 通过海绵 miR-16 抑制 miR-16 表达，而 miR-16 通过靶向 MAPK1 抑制 MAPK1 表达。此外，circZFR 通过作为 miR-16 的 ceRNA 正向调节 TC 细胞中的 MAPK1 表达。从机制上讲，在 miR-16 下调和促进 MAPK1 后，circZFR 敲低诱导的细胞活力抑制和侵袭和促进细胞凋亡被推翻。总的来说，circZFR 敲低通过海绵 miR-16 和调节 MAPK1 表达来延缓 TC 进展。CircZFR 通过海绵 miR-16 抑制 miR-16 表达，而 miR-16 通过靶向 MAPK1 抑制 MAPK1 表达。此外，circZFR 通过作为 miR-16 的 ceRNA 正向调节 TC 细胞中的 MAPK1 表达。从机制上讲，在 miR-16 下调和促进 MAPK1 后，circZFR 敲低诱导的细胞活力抑制和侵袭和促进细胞凋亡被推翻。总的来说，circZFR 敲低通过海绵 miR-16 和调节 MAPK1 表达来延缓 TC 进展。