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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

DOI https://doi.org/10.2147/OTT.S282790

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
Tel +86-13908666102
Email gxzrxl@163.com

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

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