Proteomic Characterization of the World Trade Center dust-activated mdig and c-myc signaling circuit linked to multiple myeloma.
Several epidemiological studies suggested an increased incidence rate of multiple myeloma (MM) among first responders and other individuals who exposed to World Trade Center (WTC) dust. In this report, we provided evidence showing that WTC dust is potent in inducing mdig protein and/or mRNA in bronchial epithelial cells, B cells and MM cell lines. An increased mdig expression in MM bone marrow was observed, which is associated with the disease progression and prognosis of the MM patients. Through integrative genomics and proteomics approaches, we further demonstrated that mdig directly interacts with c-myc and JAK1 in MM cell lines, which contributes to hyperactivation of the IL-6-JAK-STAT3 signaling important for the pathogenesis of MM. Genetic silencing of mdig reduced activity of the major downstream effectors in the IL-6-JAK-STAT3 pathway. Taken together, these data suggest that WTC dust may be one of the key etiological factors for those who had been exposed for the development of MM by activating mdig and c-myc signaling circuit linked to the IL-6-JAK-STAT3 pathway essential for the tumorigenesis of the malignant plasma cells.
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Kai
K
Wu
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Lingzhi
L
Li
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Chitra
C
Thakur
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Yongju
Y
Lu
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Xiangmin
X
Zhang
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Zhengping
Z
Yi
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Fei
F
Chen
D045744:Cell Line, Tumor; D049308:Dioxygenases; D004391:Dust; D056466:Histone Demethylases; D006801:Humans; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D047851:September 11 Terrorist Attacks; D015398:Signal Transduction
D004391:Dust; C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D049308:Dioxygenases; D056466:Histone Demethylases; C466777:RIOX2 protein, human