Baicalein Represses Cervical Cancer Cell Growth, Cell Cycle Progression and Promotes Apoptosis via Blocking AKT/mTOR Pathway by the Regulation of circHIAT1/miR-19a-3p Axis
Authors Hu J, Wang R, Liu Y, Zhou J, Shen K, Dai Y
Received 18 September 2020
Accepted for publication 9 December 2020
Published 9 February 2021 Volume 2021:14 Pages 905—916
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Federico Perche
Jiaojiao Hu,1,* Runkun Wang,2,* Yi Liu,3 Jianbo Zhou,4 Ka Shen,4 Yun Dai1
1Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, People’s Republic of China; 2Department of Oncology, The First People’s Hospital of Guangshui, Guangshui, People’s Republic of China; 3Department of Traditional Chinese Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, People’s Republic of China; 4Department of General Surgery, Suizhou Hospital, Hubei University of Medicine, Suizhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yun Dai
Department of Oncology, Suizhou Hospital, Hubei University of Medicine, No. 60 Longmen Street, Suizhou, 441300, People’s Republic of China
Background: Baicalein has a significant anti-cancerous function in the treatment of cervical cancer (CC). Its functional mechanism regarding circular RNA (circRNA) hippocampus abundant transcript 1 (circHIAT1) and microRNA-19a-3p (miR-19a-3p) was explored in this research.
Methods: CC cell viability and colony formation were determined using Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle progression and apoptosis were analyzed via flow cytometry. Protein markers of cell cycle, apoptosis and protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway were detected by Western blot. CircHIAT1 and miR-19a-3p levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circHIAT1 and miR-19a-3p was validated by dual-luciferase reporter and RNA pull-down assays. In vivo experiment was performed by xenograft model.
Results: CC cell growth and cell cycle progression were repressed while apoptosis was enhanced by baicalein. MiR-19a-3p was downregulated in baicalein-treated CC cells and miR-19a-3p overexpression lightened the baicalein-induced CC progression inhibition. Moreover, circHIAT1 was found to be a sponge of miR-19a-3p in CC cells. Baicalein-induced cell growth inhibition, cell cycle arrest and apoptosis promotion were neutralized by knockdown of circHIAT1 via targeting miR-19a-3p. Baicalein acted on the circHIAT1/miR-19a-3p to inactivate AKT/mTOR pathway. Baicalein also reduced CC tumor growth in vivo via regulating the levels of circHIAT1 and miR-19a-3p.
Conclusion: These findings demonstrated that the inhibitory function of baicalein in CC progression was dependent on the repression of AKT/mTOR pathway by upregulating circHIAT1 to sponge miR-19a-3p, showing a specific mechanism for baicalein in CC.
Keywords: baicalein, cervical cancer, circHIAT1, miR-19a-3p, AKT/mTOR
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]