Department of Gynecology, Shangluo Central Hospital, Shangluo City, 726000, Shaanxi Province, China.
Department of Gynaecology, Ankang Hospital of Traditional Chinese Medicine, No.47, Bashan Road(east), Hanbin District, Ankang City, 725000, Shaanxi Province, China.
BMC Cancer. 2019 Nov 8;19(1):1067. doi: 10.1186/s12885-019-6269-x.
In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells.
High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities.
The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1.
The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.
在过去的几十年中，由于环状 RNA（circRNAs）在各种癌症中的调控作用，其受到了越来越多的关注。然而，circAGFG1 如何调节宫颈癌（CC）在很大程度上仍未被发现。本研究旨在评估一种新型 circRNAs 及其相关分子机制在 CC 细胞中的作用。
通过 qRT-PCR 检测 CC 细胞或正常细胞系中 circAGFG1 的高低水平。通过功能丧失测定评估 CC 细胞的增殖和迁移能力。通过生物信息学分析和机制实验搜索并验证 circAGFG1 的下游 miRNA 和 mRNA。设计挽救实验以确认 circAGFG1/miR-370-3p/RAF1 轴在 CC 细胞活性中的作用。
与正常宫颈细胞 End1/E6E7 相比，CC 细胞中 circAGFG1 的水平丰富。评估降低 circAGFG1 水平对 CC 细胞增殖和迁移能力的抑制作用。circAGFG1 和 miR-370-3p 位于细胞质中，它们可以相互作用。此外，CC 细胞中 miR-370-3p 下调。我们还确定了 miR-370-3p 对 RAF1 的负效应。circAGFG1 可以通过吸收 miR-370-3p 促进 RAF1 表达，从而激活 RAF/MEK/ERK 通路。circAGFG1 通过海绵吸附 miR-370-3p 进一步调节 RAF1，从而促进 RAF/MEK/ERK 通路的活性，促进 CC 细胞的增殖和迁移。
本研究的结果提供了新的证据，表明 circAGFG1 在宫颈癌的增殖和迁移中起着重要的调节作用，有望将其作为 CC 治疗中诊断和治疗的潜在生物标志物。
