姜黄素通过靶向 miR-1-3p 抑制 DEN 诱导的肝癌血管生成。
Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p.
机构信息
Department of Biochemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 26 July Mehwar Road Intersection with Wahat Road, 6th of October City P.O. Box 12451, Egypt.
Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo P.O. Box 11796, Egypt.
出版信息
Int J Mol Sci. 2022 Dec 14;23(24):15904. doi: 10.3390/ijms232415904.
Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of , 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 3'-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.
肝细胞癌（HCC）的特点是其高度血管生成和转移。胸腺醌（TQ）是 的主要生物活性成分，具有抗癌和保肝作用。TQ 的抗癌作用是通过 miRNA 调节介导的。miR-1-3p 在各种癌症中发挥重要作用，但它在 HCC 侵袭性中的作用仍知之甚少。生物信息学分析预测 TIMP3 的 3'-UTR 是 miR-1-3p 的靶标；大鼠等分为四组：第 1 组为阴性对照组；第 2 组给予 TQ；第 3 组给予 DEN；第 4 组给予 DEN 预处理后。免疫组化检测大鼠肝脏中 TIMP3、MMP2、MMP9 和 VEGF 的表达。用 RT-qPCR 检测大鼠肝脏中 miR-1-3p 的水平以及转染 miR-1-3p 模拟物或抑制剂后 HepG2 细胞中 TIMP3、MMP2、MMP9 和 VEGF 的表达；在 TQ 预处理的大鼠中，检测到 MMP2、MMP9 和 VEGF 的表达下调，TIMP3 和 miR-1-3p 的表达上调。用 miR-1-3p 模拟物处理 HepG2 细胞，导致 TIMP3 上调，MMP2、MMP9 和 VEGF 下调，伤口愈合明显延迟；这些结果表明，TQ 在 HCC 中的抗血管生成作用可能是通过调节 miR-1-3p 介导的。
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