Luteolin suppresses cell migration and invasion via targeting miR-6809-5p/FLOT1/FAK and eliciting EMT in hepatocellular carcinoma

• Enclosed is our manuscript submitted for consideration in "Translational Oncology." This study investigates the migratory and invasive effects of luteolin, the active phytochemical constituent of Scutellaria barbata, on hepatocellular carcinoma (HCC) cell lines MHCC97H and Huh7, utilizing in vitro and in vivo models at cellular, animal, and molecular biological levels. Additionally, we explore the underlying regulatory mechanisms involving the miRNA6809–5p/FLOT1/FAK signaling axis and epithelial-mesenchymal transition (EMT). Our findings suggest that luteolin suppresses HCC cell migration and invasion by modulating EMT-related pathways and the miRNA6809–5p/FLOT1/FAK/PI3K/AKT/mTOR axis. • This paper was completed by our team members who invested sufficient time and effort. The authors claim that none of the material in the paper has been published or is under consideration for publication elsewhere when applying to your journal. Luteolin, 3′,4′,5,7-tetrahydroxyflavone, a natural flavonoid component found in various Chinese herbs such as Scutellaria barbata D. Don, honeysuckle, chrysanthemum, schizonepeta, and ajuga decumbens, exhibits potential for cancer prevention and therapy. This study elucidates the molecular mechanisms by which luteolin, an active constituent of Scutellaria barbata, inhibits invasion and metastasis of hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The oncogenic microRNA miR-6809–5p was found to be aberrantly upregulated in HCC tissues and downregulated by luteolin in HCC cells; overexpression of miR-6809–5p was able to restore the anti-HCC effects of luteolin via the miR-6809–5p/FLOT1/FAK signaling pathway. Furthermore, luteolin suppressed HCC invasion, metastasis, and epithelial-mesenchymal transition (EMT) through modulation of the PI3K/AKT/mTOR pathway, affecting markers such as E-cadherin, β-catenin, Vimentin, N-cadherin, Snail, Twist, and Slug. This research demonstrates that luteolin effectively inhibits HCC cell migration and invasion and significantly suppresses epithelial mesenchymal transition (EMT) both in vitro and in vivo.