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hsa_circ_0007874 的上调通过调节 miR-760/SOCS3 通路抑制卵巢癌的进展。

Upregulation of hsa_circ_0007874 suppresses the progression of ovarian cancer by regulating the miR-760/SOCS3 pathway.

机构信息

Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, China.

出版信息

Cancer Med. 2020 Apr;9(7):2491-2499. doi: 10.1002/cam4.2866. Epub 2020 Feb 5.

Abstract

Ovarian cancer (OVA) is a fatal and common malignancy in women worldwide. Circular RNAs (circRNAs) consist of a family of circular endogenous RNAs generated by selective splicing, and they are involved in many diseases. Previous studies reported that hsa_circ_0007874 is aberrantly expressed in cancer and functions in tumorigenesis. While the hsa_circ_0007874 role in OVA is unclear. Here, we detected the hsa_circ_0007874 expression in OVA cell lines using Rt-qPCR. Hsa_circ_0007874 subcellular localization was confirmed by fluorescence in situ hybridization. The relationship between hsa_circ_0007874, microRNAs (miRNAs), and relative protein levels was assessed using the luciferase reporter assays. Results verified that hsa_circ_0007874 is downregulated in OVA cell lines. hsa_circ_0007874 overexpression decreased the OVA cell migration and proliferation in vitro and in vivo. Bioinformatics and luciferase reporter assays confirmed that miR-760 and SOCS3 are the downstream targets of hsa_circ_0007874. Downregulation of SOCS3 or miR-760 overexpression restored the migration and proliferation ability of SKOV3 or A2780 cells overexpressing hsa_circ_0007874. Downregulation of SOCS3 restored the proliferation and migration in miR-760 knockdown SKOV3 and A2780 cells. In summary, the data suggest that hsa_circ_0007874 acts as a tumor suppressor by regulating the miR-760/SOCS3 axis, highlighting its potential as an effective therapeutic target for OVA.

摘要

卵巢癌(OVA)是全球女性中一种致命且常见的恶性肿瘤。环状 RNA(circRNA)由选择性剪接产生的一类环状内源性 RNA 组成,它们参与许多疾病的发生。先前的研究报道 hsa_circ_0007874 在癌症中表达异常,并在肿瘤发生中发挥作用。然而,hsa_circ_0007874 在 OVA 中的作用尚不清楚。在这里,我们使用 Rt-qPCR 检测了 OVA 细胞系中的 hsa_circ_0007874 表达。通过荧光原位杂交证实 hsa_circ_0007874 的亚细胞定位。使用荧光素酶报告基因检测评估 hsa_circ_0007874、microRNAs(miRNAs)和相对蛋白水平之间的关系。结果验证了 hsa_circ_0007874 在 OVA 细胞系中下调。hsa_circ_0007874 过表达可降低 OVA 细胞体外和体内的迁移和增殖。生物信息学和荧光素酶报告基因检测证实 miR-760 和 SOCS3 是 hsa_circ_0007874 的下游靶标。下调 SOCS3 或过表达 miR-760 可恢复过表达 hsa_circ_0007874 的 SKOV3 或 A2780 细胞的迁移和增殖能力。下调 miR-760 可恢复 miR-760 敲低的 SKOV3 和 A2780 细胞中的增殖和迁移。总之,数据表明 hsa_circ_0007874 通过调节 miR-760/SOCS3 轴发挥肿瘤抑制作用,凸显其作为 OVA 有效治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c8/7131836/fb0a7ac97631/CAM4-9-2491-g001.jpg

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