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环状 RNA hsa_circRNA_101996 通过抑制 miR-8075 来激活 TPX2 的表达,从而增加宫颈癌的增殖和侵袭。

CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075.

机构信息

Department of Obstetrics and Gynecology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

J Cell Physiol. 2019 Aug;234(8):14296-14305. doi: 10.1002/jcp.28128. Epub 2019 Jan 11.

Abstract

In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR-8075, which targeted TPX2 in cervical cancer cells. We showed that miR-8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996-mediated inhibition of miR-8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996-miR-8075-TPX2 network promoted cervical cancer progression.

摘要

近年来,环状 RNA 已被证明在多种人类癌症中作为重要的调节剂发挥作用。然而,环状 RNA 在宫颈癌中的功能和机制仍不清楚。在本研究中,我们通过生物信息学分析表明,hsa_circRNA_101996 在宫颈癌组织中的表达水平明显高于配对的正常组织。我们还发现,hsa_circRNA_101996 在宫颈癌组织中的表达水平与 TNM 分期、肿瘤大小和淋巴结转移呈正相关。此外,hsa_circRNA_101996 水平较高与宫颈癌患者的不良预后相关。我们发现,hsa_circRNA_101996 的敲低显著抑制了宫颈癌细胞的增殖、细胞周期、迁移和侵袭。在机制上,我们证明 hsa_circRNA_101996 作为 miR-8075 的海绵,在宫颈癌细胞中靶向 TPX2。我们还发现,在宫颈癌组织中下调的 miR-8075 抑制了宫颈癌细胞的增殖、迁移和侵袭。此外,我们验证了 hsa_circRNA_101996 通过抑制 miR-8075 而上调的 TPX2 促进了宫颈癌的增殖、迁移和侵袭。总之,我们的研究结果揭示了 hsa_circRNA_101996-miR-8075-TPX2 网络促进宫颈癌进展的新机制。

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