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SRC3 expressed in bone marrow mesenchymal stem cells promotes the development of multiple myeloma

查看全文 作  者:Jie [1]Jin;Shidi [2]Cheng;Yu [2]Wang;Tao [2]Wang;Dongfeng [1]Zeng;Zheng [1]Li;Xiang [1]Li;Jin [1]Wang 高影响力作者 机构地区:[1]Department of Hematology,the Third affiliated Daping Hospital,Army Medical University,Chongqing 400038,China;[2]Institute of Combined Injury,State Key Laboratory ofTrauma,Burns and Combined Injury,College of Preventive Medicine,Army Medical University,Chongqing 400038,China高影响力机构 出  处:《Acta Biochimica et Biophysica Sinica》索引2019年第51卷第12期,共9页高影响力期刊 基  金:This work was supported by the grant from the National Science Fund for Young Scholars(No.81500175). 摘  要:SRC3 plays critical roles in various biological processes of diseases,including proliferation,apoptosis,migration,and cell cycle arrest.However,the effect of SRC3 expression in mesenchymal stem cells(MSCs)on multiple myeloma(MM)is not clear yet.In our study,MSCs(MSC-SRC3,MSCSRC3-/-)and MM cells were co-cultured in a direct or indirect way.The proliferation of MM cells was studied by CCK-8 and colony formation assays.The apoptosis and cell cycle of MM cells were detected by flow cytometry.In addition,the expressions of proteins in MM cells were detected by western blot analysis and the secretions of cytokines were measured by ELISA.Our data showed that the expression of SRC3 in bone marrow mesenchymal stem cells(BM-MSCs)could promote cell proliferation and colony formation of MM cells through accelerating the transformation of the G1/S phase,no matter what kind of culture method was adopted.Meanwhile,SRC3 expressed in BM-MSCs could inhibit the apoptosis of MM cells through the caspase apoptosis pathway and mitochondrial apoptosis pathway.Moreover,SRC3 could enhance the adhesion ability of MM cells through up-regulating the expression of adhesion molecules including CXCL4,ICAM1,VLA4,and syndecan-1.SRC3 also played a regulatory role in the progress of MM through the NF-kB and Pl-3K/Akt pathways.SRC3 expressed in MSCs was found to promote the growth and survival of MM cells,while SRC3 silencing in MSCs could inhibit the development of MM.These results would be useful for developing a more effective new strategy for MM treatment. 关 键 词:SRC3 bone MARROW MESENCHYMAL stem cells(BM-MSCs) multiple myeloma(MM) growth SURVIVAL
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