title: Activation of LTBP3 gene by a long noncoding RNA (lncRNA) MALAT1 transcript in mesenchymal stem cells from multiple myeloma.
abstract: Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules in tumor suppressor and oncogenic pathways. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. Here we explored the biology of the lncRNA MALAT1 and considered the potential significance in mesenchymal stem cells from myeloma patients. By using assays such as RNA interference, luciferase, chromatin immunoprecipitation, and RNA immunoprecipitation, we showed that in mesenchymal stem cells MALAT1 promoted the activation effect of the key transcription factor Sp1 on LTBP3 promoter by modulating recruitment of Sp1 to the LTBP3 gene that regulated the bioavailability of TGF-β in particular. Our data suggested that lncRNA MALAT1 directly interacted with Sp1 and LTBP3 promoter to increase expression of LTBP3 gene. The specificity and efficiency of activation were ensured by the formation of a stable complex between MALAT1 and the LTBP3 promoter, direct interaction of MALAT1 with Sp1, and recruitment of Sp1 to the promoter. In this study, we showed that the mechanism of transcriptional activation of LTBP3 promoter depended on MALAT1 initiated from neighboring gene LTBP3 and involved both the direct interaction of the Sp1 and promoter-specific activation. Our knowledge of the role of MALAT1 in cellular transformation is pointing toward its potential use as a biomarker and a target for novel therapeutic approaches in multiple myeloma.
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Bingzong
authors.initials: B
authors.lastname: Li
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: the Department of Cell Biology, School of Biology and Basic of Medical Science, Soochow University, Suzhou 215123, and.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.affiliation: the Department of Cell Biology, School of Biology and Basic of Medical Science, Soochow University, Suzhou 215123, and.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: the Department of Molecular Biology, Medical Ecsomatics College of Beihua University, Jinlin 132013, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Fu
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Department of Haematology, the Second Affiliated Hospital of Soochow University, Suzhou 215006.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: the Department of Cell Biology, School of Biology and Basic of Medical Science, Soochow University, Suzhou 215123, and zhuangwenzhuo@suda.edu.cn.
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Zhuang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C509038:LTBP3 protein, human; D053779:Latent TGF-beta Binding Proteins; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D016329:Sp1 Transcription Factor
keywords: Biomarker; Mesenchymal Stem Cells (MSCs); Multiple Myeloma; RNA; Transcription