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

• Published in: Molecular therapy. Nucleic acids Vol. 20; pp. 308 - 322
• Main Authors: Ou, Rongying, Mo, Laiming, Tang, Huijing, Leng, Shaolong, Zhu, Haiyan, Zhao, Liang, Ren, Yi, Xu, Yunsheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.06.2020; American Society of Gene & Cell Therapy; Elsevier
• Subjects: AKT1; cervical cancer; circ-AKT1; miR-942-5p; AKT1; circ-AKT1; cervical cancer; miR-942-5p
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.01.003

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.