Abstract:
Hepatocellular 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.
