Luteolin suppresses lung cancer progression through targeting the circ_0000190/miR-130a-3p/notch-1 signaling pathway

Abstract

Lung cancer is the leading cause of cancer mortality worldwide. Luteolin has been reported to repress the development of lung cancer. And circular RNAs (circRNAs) circ_0000190 was upregulated in lung cancer tissues. This study is designed to explore the roles of luteolin and circ_0000190 in lung cancer progression. Cell viability, colony number, migration, invasion, and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. The lactate dehydrogenase (LDH) release was determined by special kits. Protein levels of B-celllymphoma-2 (Bcl-2) Cleaved-caspase3 (casp3), Bcl-2 related X protein (Bax), Notch-1, hairy enhance of split-1(Hes-1), and vascular endothelium growth factor (VEGF) were determined by western blot assay. Circ_0000190 andmicroRNA-130a-3p (miR-130a-3p) expression were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The binding relationship between circ_0000190 andmiR-130a-3pwas predicted by starbase and then verified by a dual-luciferase reporter and RNA pull-down assays. The biological roles of Luteolin and circ_0000190 on tumor growth of lung cancer were examined by the xenograft tumor model in vivo. Luteolin inhibited cell viability, colony formation, migration, invasion, and promoted apoptosis of lung cancer cells. Moreover, overexpression of circ_0000190 could counteract the suppression role of luteolin on lung cancer development. Andcirc_0000190 directly bound with miR-130a-3p. Luteolin blocked lung cancer cell growth, metastasis, and Notch-1 signaling pathway by modulating the circ_0000190/miR-130a-3pin vitro. Luteolin repressed tumor growth of lung cancer in vivo by regulating circ_0000190. Luteolin dampened the progression of lung cancer partly by regulating circ_0000190/miR-130a-3p, providing an underlying therapeutic target for lung cancer.

Keywords:

• Luteolin
• circ_0000190
• miR-130a-3p
• Notch-1
• lung cancer

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Funding

This work was supported by 2020 Provincial Medical and Health Sciences Technical Plan Project (Innovative Talent Support Project) (2020KY1076).