The human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer

Yadong Zhang, Yongju Lu, Bao Zhu Yuan, Vince Castranova, Xianglin Shi, John L. Stauffer, Laurence M. Demers, Fei Chen

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4873-4882
Number of pages10
JournalOncogene
Volume24
Issue number31
DOIs
StatePublished - Jul 21 2005

Bibliographical note

Funding Information:
This work was partially supported by the United States Bureau of Mines, Generic Mineral Technology Center for Respiratory Dust Grant G1145242 to LM Demers and a Career Development Award under a cooperative agreement from the Centers for Disease Control and Prevention through the Association of Teachers of Preventive Medicine to F Chen. The DDRT–PCR, cloning, and DNA sequencing were conducted by Y Lu and F Chen when both of them were employees of the Pennsylvania State University College of Medicine at Hershey during July, 1994 to June, 1998. We thank Dr Murali Rao and Mr Terry Meighan in the Pathology and Physiology Research Branch at the National Institute for Occupational Safety and Health for their gift of total RNA from A549 cells and the mdig siRNA they purchased.

Keywords

  • Lung cancer
  • Mineral dust
  • mdig

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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