title: miR-15a/16-1 enhances retinoic acid-mediated differentiation of leukemic cells and is up-regulated by retinoic acid.
abstract: miR-15a and miR-16-1 (miR-15a/16-1) have been implicated in apoptosis, cell cycle regulation and chemosensitivity of tumor cells, but little is known about the role of miR-15a/16-1 in the differentiation of leukemic cells. In this study, we found that the expression level of miR-15a/16-1 was up-regulated by all-trans retinoic acid (ATRA) treatment in NB4, HL-60 and U937 cell lines and primary leukemic cells. Overexpression of miR-15a/16-1 could not directly drive cells to undergo differentiation but enhanced ATRA-induced differentiation in NB4 and U937 cells. Up-regulation of miR-15a/16-1 was also observed in 36 patients with acute myeloid leukemia (AML) who achieved a complete remission (CR), and two of them showed sharp down-regulation of miR-15a/16-1 when they had a molecular relapse. These data indicate that miR-15a/16-1 plays an important role in the ATRA-induced differentiation of leukemic and primary AML cells.
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Shen-Meng
authors.initials: SM
authors.lastname: Gao
authors.forename: Junjun
authors.initials: J
authors.lastname: Yang
authors.forename: Chiqi
authors.initials: C
authors.lastname: Chen
authors.forename: Shenghui
authors.initials: S
authors.lastname: Zhang
authors.forename: Chong-Yun
authors.initials: CY
authors.lastname: Xing
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D014212:Tretinoin