The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer.
Environmental or occupational exposure to mineral dusts, mainly silica and asbestos, is associated with an increased incidence of lung inflammation, fibrosis, and/or cancer. To better understand the molecular events associated with these pulmonary diseases, we attempted to identify genes that are regulated by mineral dusts. Using a differential display reverse transcription polymerase chain reaction technique and mRNAs of alveolar macrophages from both normal individuals and coal miners, we identified a novel mineral dust-induced gene named mdig, which had not been fully characterized. The expression of mdig mRNA was detected in alveolar macrophages from coal miners but not from normal subjects. The inducible expression of mdig could be observed in A549 cells exposed to silica particles in a time-dependent manner. The full-length mdig mRNA was expressed in human lung cancer tissues but was barely detectable in the adjacent normal tissues. In addition, a number of lung cancer cell lines constitutively express mdig. Alternative spliced transcripts of mdig were detected in some lung cancer cell lines. Silencing mdig mRNA expression in A549 lung cancer cells by siRNA-mediated RNA interference inhibits cell proliferation and sensitizes the cells to silica-induced cytotoxicity. These results suggest that the mdig gene may be involved in the regulation of cell growth and possibly the development of cancer.
Zhang
Yadong
Y
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
Lu
Yongju
Y
Yuan
Bao-Zhu
BZ
Castranova
Vince
V
Shi
Xianglin
X
Stauffer
John L
JL
Demers
Laurence M
LM
Chen
Fei
F
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division; D045744:Cell Line, Tumor; D003032:Coal Mining; D049308:Dioxygenases; D005091:Exons / Q000235:genetics; D056466:Histone Demethylases; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D012016:Reference Values; D012822:Silicon Dioxide / Q000633:toxicity; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012822:Silicon Dioxide; D049308:Dioxygenases; D056466:Histone Demethylases; C466777:RIOX2 protein, human