Tadros, Samer AAttia, Yasmin M.Maurice, Nadine W.Fahim, Sally A.Abdelwahed, Fatma M.Ibrahim, SamarBadary, Osama A. R2022-12-252022-12-252022-11https://doi.org/10.3390/ ijms232415904 Academic Editors: Karel Smetana, Jr. and Michal Masarik Receivedhttp://repository.msa.edu.eg/xmlui/handle/123456789/5301Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of Nigella sativa, has shown anticancer and hepatoprotective effects. TQ’s anticancer effect is mediated through miRNA regulation. miR-1-3p plays a significant role in various cancers but its role in HCC invasiveness remains poorly understood. Bio-informatics analysis predicted that the 30 -UTR of TIMP3 is a target for miR-1-3p; Rats were equally divided into four groups: Group 1, the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received DEN after pretreatment with TQ. The expression of TIMP3, MMP2, MMP9, and VEGF in rats’ liver was determined immunohistochemically. RT-qPCR was used to measure the miR-1-3p level in rats’ liver, and TIMP3, MMP2, MMP9, and VEGF in the HepG2 cells after being transfected with miR-1-3p mimic or inhibitor; In rats pretreated with TQ, a decreased expression of MMP2, MMP9 and VEGF, and increased expression levels of TIMP3 and miR-1-3p were detected. Treating the HepG2 cells with miR-1-3p mimic led to the upregulation of TIMP3 and downregulation of MMP2, MMP9, and VEGF, and showed a significant delay in wound healing; These results suggested that the anti-angiogenic effect of TQ in HCC may be mediated through the regulation of miR-1-3p.en-USthymoquinone;diethylnitrosamine;miR-1-3p;angiogenesis;TIMP3; liver cancerArticlehttps://doi.org/10.3390/