Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p
Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of <i>Nigella sativa</i>, has shown anticancer and hepatoprotective effects. TQ’s anticancer effect is mediated through miRNA regulation. miR-1-3p pl...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15904 |
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| author | Samer A. Tadros Yasmin M. Attia Nadine W. Maurice Sally A. Fahim Fatma M. Abdelwahed Samar Ibrahim Osama A. Badary |
| author_facet | Samer A. Tadros Yasmin M. Attia Nadine W. Maurice Sally A. Fahim Fatma M. Abdelwahed Samar Ibrahim Osama A. Badary |
| author_sort | Samer A. Tadros |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of <i>Nigella sativa</i>, 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. |
| first_indexed | 2024-03-09T16:19:15Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:15Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ee4d5fa273694afcaf85167fd6c02b592023-11-24T15:30:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241590410.3390/ijms232415904Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3pSamer A. Tadros0Yasmin M. Attia1Nadine W. Maurice2Sally A. Fahim3Fatma M. Abdelwahed4Samar Ibrahim5Osama A. Badary6Department 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, EgyptPharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo P.O. Box 11796, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box 11562, EgyptDepartment of Biochemistry, School of Pharmacy, Newgiza University (NGU), Newgiza, Km 22 Cairo-Alexandria Desert Road, Giza P.O. Box 12577, EgyptMedical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo P.O. Box 11796, EgyptClinical Pharmacy Practice Department, Ahram Canadian University, 4th Industrial Zone, Banks Complex, 6th of October City P.O. Box 12451, EgyptClinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo P.O. Box 12508, EgyptHepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of <i>Nigella sativa</i>, 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.https://www.mdpi.com/1422-0067/23/24/15904thymoquinonediethylnitrosaminemiR-1-3pangiogenesisTIMP3liver cancer |
| spellingShingle | Samer A. Tadros Yasmin M. Attia Nadine W. Maurice Sally A. Fahim Fatma M. Abdelwahed Samar Ibrahim Osama A. Badary Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p International Journal of Molecular Sciences thymoquinone diethylnitrosamine miR-1-3p angiogenesis TIMP3 liver cancer |
| title | Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p |
| title_full | Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p |
| title_fullStr | Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p |
| title_full_unstemmed | Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p |
| title_short | Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p |
| title_sort | thymoquinone suppresses angiogenesis in den induced hepatocellular carcinoma by targeting mir 1 3p |
| topic | thymoquinone diethylnitrosamine miR-1-3p angiogenesis TIMP3 liver cancer |
| url | https://www.mdpi.com/1422-0067/23/24/15904 |
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