title: miR-196b/miR-1290 participate in the antitumor effect of resveratrol via regulation of IGFBP3 expression in acute lymphoblastic leukemia.
abstract: MicroRNAs play critical roles in the progression of acute lymphoblastic leukemia (ALL). Previous studies have indicated that miR-196b and miR-1290 play critical roles in T-cell ALL (T-ALL) and B-cell ALL (B-ALL), respectively. Resveratrol, a natural edible polyphenolic phytoalexin, possesses certain anticancer activities. Nevertheless, the mechanism involved in the regulation of ALL by resveratrol is still poorly understood. The present study aimed to reveal the potential mechanism underlying the antitumor effect of resveratrol in ALL focusing on miRNAs. Research indicates that insulin-like growth factor binding protein 3 (IGFBP3) plays a critical role in the aetiology of ALL. In the present study, we first demonstrated that the expression of IGFBP3 was decreased in ALL patients. We further identified that miR-196b and miR-1290 were overexpressed in T-ALL TALL-104 and B-ALL SUP-B15 cell lines, respectively. Moreover, resveratrol markedly decreased the overexpression of miR-196b/miR-1290 and elevated IGFBP3 expression in the ALL cell lines. As an miR-196b/miR-1290 inhibitor, resveratrol was further demonstrated to exert antitumor effects on ALL cells including antiproliferation, cell cycle arrest, apoptosis and inhibition of migration. Dual-luciferase reporter assay revealed that miR-196b/miR-1290 directly bound to the 3'-untranslated (3'-UTR) region of IGFBP3 mRNA. Moreover, we observed that IGFBP3 short interfering RNA reversed the antitumor activity of resveratrol against ALL cells. Taken together, the present study provides evidence that resveratrol targets miR-196b and miR-1290 for its antitumor activity in T-ALL and B-ALL, respectively. The present study also confirms that both miR‑196b and miR-1290 target the IGFBP3 3'-UTR and are potential therapeutic targets for ALL.
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Shunqing
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ying
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Mao
mesh_terms: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D034741:RNA, Small Interfering; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C574604:MIRN1290 microRNA, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D013267:Stilbenes; D000077185:Resveratrol