title: Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells.
abstract: The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM) cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6) produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.
authors.forename: Mu
authors.initials: M
authors.lastname: Hao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: An
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sui
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Dehui
authors.initials: D
authors.lastname: Zou
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D035683:MicroRNAs