OncoTargets and Therapy (Feb 2021)
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
Abstract
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 workCorrespondence: Yun DaiDepartment of Oncology, Suizhou Hospital, Hubei University of Medicine, No. 60 Longmen Street, Suizhou, 441300, People’s Republic of ChinaTel +86-13908666102Email [email protected]: 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
