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circRNA-AKT1 Sequesters miR-942-5p to Upregulate AKT1 and Promote Cervical Cancer Progression.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.omtn.2020.01.003
Rongying Ou 1 , Laiming Mo 2 , Huijing Tang 3 , Shaolong Leng 3 , Haiyan Zhu 4 , Liang Zhao 5 , Yi Ren 6 , Yunsheng Xu 7
Affiliation  

Statistics show that the prognosis of cervical cancer (CC) is poor, and the death rate of CC in advanced stage has been rising in recent years. Increasing evidence has demonstrated that circular RNAs (circRNAs) serve as promising biomarkers in human cancers, including CC. The present study planned to find out the circRNA involved in CC and to explore its regulatory mechanism in CC. We discovered the new circRNA, circ-0033550, upregulated in CC. Its associated gene was AKT (also known as protein kinase B) serine/threonine kinase 1 (AKT1), so we renamed circ-0033550 as circ-AKT1. We confirmed the high expression of circ-AKT1 in CC samples and cell lines, as well as the circle structure of circ-AKT1. Functionally, gain- and loss-of-function experiments indicated that circ-AKT1 and AKT1 promoted CC cell proliferation and invasion. Moreover, circ-AKT1 and AKT1 were induced by transforming growth factor beta (TGF-β) and facilitated EMT (epithelial-mesenchymal transition) in CC. Mechanically, we illustrated that circ-AKT1 upregulated AKT1 by sponging miR-942-5p. Rescue assays confirmed the role of the circ-AKT1/miR-942-5p/AKT1 axis in CC progression. In vivo assays validated that circ-AKT1 promoted tumor growth in CC. Overall, circRNA-AKT1 sequestered miR-942-5p to upregulate AKT1 and promote CC progression, which may offer a new molecular target for the treatment improvement of CC.



中文翻译:

circRNA-AKT1隔离miR-942-5p以上调AKT1并促进宫颈癌的进展。

据统计,近年来宫颈癌的预后较差,晚期CC的死亡率不断上升。越来越多的证据表明,环状RNA(circRNA)在包括CC在内的人类癌症中可作为有前途的生物标记。本研究计划找出参与CC的circRNA,并探讨其在CC中的调控机制。我们发现了在CC中上调的新circRNA,circ-0033550。它的相关基因是AKT(也称为蛋白激酶B)丝氨酸/苏氨酸激酶1(AKT1),因此我们将circ-0033550重命名为circ-AKT1。我们证实了circ-AKT1在CC样品和细胞系中的高表达,以及circ-AKT1的环状结构。功能上,功能获得和丧失的实验表明,circ-AKT1和AKT1促进CC细胞增殖和侵袭。此外,circ-AKT1和AKT1通过转化生长因子β(TGF-β)诱导并促进CC中的EMT(上皮-间质转化)。在机械上,我们举例说明了circ-AKT1通过海绵miR-942-5p上调了AKT1。救援试验证实了circ-AKT1 / miR-942-5p / AKT1轴在CC进展中的作用。体内试验验证了circ-AKT1促进了CC中肿瘤的生长。总体而言,circRNA-AKT1隔离miR-942-5p以上调AKT1并促进CC进程,这可能为CC的治疗改善提供新的分子靶标。

更新日期:2020-01-16
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