{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T05:12:26Z","timestamp":1747199546442,"version":"3.40.5"},"reference-count":44,"publisher":"Akademiai Kiado Zrt.","funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"crossref","award":["RGP.1\/163\/43"],"award-info":[{"award-number":["RGP.1\/163\/43"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["akjournals.com"],"crossmark-restriction":true},"short-container-title":["PhysInt"],"published-print":{"date-parts":[[2022,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n            <jats:p>Scientific efforts have been made for a better understanding of the pathogenesis of hepatocellular carcinoma (HCC). We investigated the possible role of miR-192\/nuclear factor-\u03baB (NF-\u03baB)\/transforming growth factor-\u03b2 (TGF-\u03b2)\/E-cadherin in hepatic tumorigenesis. We expected a modulatory impact of thymoquinone. Thirty adult male rats were assigned into 3 groups (<jats:italic>n<\/jats:italic> = 10); (1) Control group. Group (2): Experimental HCC induced by intraperitoneal injection of diethylnitrosamine (DENA) followed by carbon tetrachloride (CCl4). Group (3): Thymoquinone 20\u2009mg kg<jats:sup>\u22121<\/jats:sup>\/oral supplementation starting from the model induction to the end of the 8th week. The HCC (DENA-CCL4) model was confirmed by elevated serum levels of alpha-fetoprotein and transaminases (ALT, AST) and by histopathological examination which denoted marked cellular atypia and features of neoplasia. Suppressed hepatic miR-192 and E-cadherin expression were detected in the HCC (DENA-CCL4) group accompanied by elevated tumor necrosis factor (TNF-\u03b1), interleukin (IL6)\/NF-\u03baB &amp; TGF-\u03b21. Thymoquinone treatment protected the rat livers from hepatic tumorigenesis. Thymoquinone diminished (<jats:italic>P<\/jats:italic> &lt; 0.001) alpha-fetoprotein and improved ALT, AST. It preserved hepatic miR-192 and normal E-cadherin expression. Thymoquinone-treated rats showed abrogated TNF-\u03b1, IL6\/NF-\u03baB\/TGF-\u03b2. Thymoquinone increased cell apoptosis markers Bax\/Bcl2 and diminished cellular atypia. Pearson's correlations revealed positive association between miR-192 expression and E-cadherin and Bax\/Bcl2 as well, and it was negatively correlated to alpha-fetoprotein, NF-\u03baB and TGF-\u03b2 and the cellular atypia score. In conclusion, thymoquinone protected the liver tissues through preserving miR-192 and E-cadherin and aborting NF-\u03baB &amp; TGF-\u03b2 signaling. The current results highlight a new role for thymoquinone in preventing hepatic tumorigenesis.<\/jats:p>","DOI":"10.1556\/2060.2022.00163","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T07:37:45Z","timestamp":1661326665000},"update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.1","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of miR-192\/NF-\u03baB\/ TGF-\u03b2\/ E-cadherin by thymoquinone protects against diethylnitrosamine \/carbon tetrachloride hepatotoxicity"],"prefix":"10.1556","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5423-7228","authenticated-orcid":true,"given":"Hend","family":"Ashour","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia"},{"name":"Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha Eid","family":"Farghaly","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akef Abdelhalim","family":"Khowailed","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basma Emad","family":"Aboulhoda","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila Ahmed","family":"Rashed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Mahmoud","family":"Elsebaie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safy Salah","family":"Gaber","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"425","reference":[{"issue":"5","key":"B1","series-title":"J Cancer Res Clin Oncol","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s00432-017-2364-z","article-title":"Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine","volume":"143","author":"Ding \n                     YF","year":"2017","unstructured":"Ding \n                     YF\n                  , \n                     Wu \n                     ZH\n                  , \n                     Wei \n                     YJ\n                  , \n                     Shu \n                     L\n                  , \n                     Peng \n                     YR\n                  \n               . 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Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology \n               2013; 144(3): 512\u201327. https:\/\/doi.org\/10.1053\/j.gastro.2013.01.002.10.1053\/j.gastro.2013.01.002"},{"key":"B3","series-title":"Crit Rev Oncol Hematol","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.critrevonc.2017.11.010","article-title":"E-cadherin: Its dysregulation in carcinogenesis and\u00a0clinical implications","volume":"121","author":"Wong \n                     SHM","year":"2018","unstructured":"Wong \n                     SHM\n                  , \n                     Fang \n                     CM\n                  , \n                     Chuah \n                     LH\n                  , \n                     Leong \n                     CO\n                  , \n                     Ngai \n                     SC\n                  \n               . E-cadherin: Its dysregulation in carcinogenesis and\u00a0clinical implications. Crit Rev Oncol Hematol \n               2018; 121: 11\u201322. https:\/\/doi.org\/10.1016\/j.critrevonc.2017.11.010.10.1016\/j.critrevonc.2017.11.010"},{"issue":"5","key":"B4","series-title":"World J Gastroenterol","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3748\/wjg.15.513","article-title":"Dysregulation of apoptosis in hepatocellular carcinoma cells","volume":"15","author":"Fabregat \n                     I","year":"2009","unstructured":"Fabregat \n                     I\n                  \n               . Dysregulation of apoptosis in hepatocellular carcinoma cells. 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Tumour Biol \n               2016; 37(1): 115\u201325. https:\/\/doi.org\/10.1007\/s13277-015-4374-2.10.1007\/s13277-015-4374-2"},{"issue":"10","key":"B9","series-title":"Carcinogenesis","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1093\/carcin\/bgt184","article-title":"miR-192, miR-194 and miR-215: A\u00a0convergent microRNA network suppressing tumor progression in renal cell carcinoma","volume":"34","author":"Khella \n                     HW","year":"2013","unstructured":"Khella \n                     HW\n                  , \n                     Bakhet \n                     M\n                  , \n                     Allo \n                     G\n                  , \n                     Jewett \n                     MA\n                  , \n                     Girgis \n                     AH\n                  , \n                     Latif \n                     A\n                  , et\u00a0al.\n                \n               miR-192, miR-194 and miR-215: A\u00a0convergent microRNA network suppressing tumor progression in renal cell carcinoma. 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Nucleic Acids Res \n               2011; 39(15): 6669\u201378. https:\/\/doi.org\/10.1093\/nar\/gkr232.10.1093\/nar\/gkr232"},{"issue":"11","key":"B11","series-title":"Tumour Biol","doi-asserted-by":"publisher","first-page":"15211","DOI":"10.1007\/s13277-016-5417-z","article-title":"Upregulation of miR-192 inhibits cell growth and invasion and induces cell apoptosis by targeting TCF7 in human osteosarcoma","volume":"37","author":"Wang \n                     Y","year":"2016","unstructured":"Wang \n                     Y\n                  , \n                     Zhang \n                     S\n                  , \n                     Xu \n                     Y\n                  , \n                     Zhang \n                     Y\n                  , \n                     Guan \n                     H\n                  , \n                     Li \n                     X\n                  , et\u00a0al.\n                \n               Upregulation of miR-192 inhibits cell growth and invasion and induces cell apoptosis by targeting TCF7 in human osteosarcoma. Tumour Biol \n               2016; 37(11): 15211\u201320. https:\/\/doi.org\/10.1007\/s13277-016-5417-z.10.1007\/s13277-016-5417-z"},{"issue":"1","key":"B12","series-title":"Infect Agent Cancer","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13027-019-0226-9","article-title":"Dissecting the roles of thymoquinone on the prevention and the treatment of hepatocellular carcinoma: An overview on the current state of knowledge","volume":"14","author":"Bimonte \n                     S","year":"2019","unstructured":"Bimonte \n                     S\n                  , \n                     Albino \n                     V\n                  , \n                     Barbieri \n                     A\n                  , \n                     Tamma \n                     ML\n                  , \n                     Nasto \n                     A\n                  , \n                     Palaia \n                     R\n                  , et\u00a0al.\n                \n               Dissecting the roles of thymoquinone on the prevention and the treatment of hepatocellular carcinoma: An overview on the current state of knowledge. 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