title: Sprouty2 regulates proliferation and survival of multiple myeloma by inhibiting activation of the ERK1/2 pathway in vitro and in vivo.
abstract: Multiple myeloma (MM) is an incurable disease, and its pathogenesis remains unclear. MicroRNA (miR)-21 was detected at a high level in MM and plays a key role in the pathogenesis of MM. However, Sprouty2 (spry2), a downstream target of miR-21, has low expression, and its mechanism in MM is unknown. We investigated whether spry2 could exert an antimyeloma effect and further studied the potential pathogenesis and progression of MM. To address the functional consequences of spry2, we assessed the expression levels of spry2 in several myeloma cell lines and detected low expression levels in MM cells. Overexpression of spry2 suppressed growth and colony formation ability and decreased the phosphorylation of extracellular signal-regulated kinases 1 and 2. Spry2 also decreased secretion of vascular endothelial growth factor and partially enhanced the sensitivity of MM cells to an inhibitor of mitogen-activated protein kinases 1 and 2. Additionally, spry2 inhibited the tumorigenesis and angiogenesis of MM cells in vivo. In summary, we report for the first time that spry2 can inhibit MM cell growth and survival with a concomitant reduction in phosphorylation of extracellular signal-regulated kinases 1 and 2 in vitro and in vivo.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Luo
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xia
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China. Electronic address: lihmd@163.com.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; C485561:SPRY2 protein, human; D042461:Vascular Endothelial Growth Factor A