circRNA-AKT1 Sequesters miR-942-5p to Upregulate AKT1 and Promote Cervical Cancer Progression

Rongying Ou; Laiming Mo; Huijing Tang; Shaolong Leng; Haiyan Zhu; Liang Zhao; Yi Ren; Yunsheng Xu

doi:10.1016/j.omtn.2020.01.003

circRNA-AKT1 Sequesters miR-942-5p to Upregulate AKT1 and Promote Cervical Cancer Progression

Mol Ther Nucleic Acids. 2020 Jun 5:20:308-322. doi: 10.1016/j.omtn.2020.01.003. Epub 2020 Jan 16.

Authors

Rongying Ou¹, Laiming Mo², Huijing Tang³, Shaolong Leng³, Haiyan Zhu⁴, Liang Zhao⁵, Yi Ren⁶, Yunsheng Xu⁷

Affiliations

¹ Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Clinical Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
³ Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁴ Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁵ Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁶ Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA.
⁷ Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. Electronic address: shengqix730369@163.com.

Abstract

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.

Keywords: AKT1; cervical cancer; circ-AKT1; miR-942-5p.