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

Our plain-English summary of The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer, by Y. Zhang, Y. Lu, B.Z. Yuan, et al (Oncogene, 2005).

The study

• Authors: Y. Zhang, Y. Lu, B.Z. Yuan, V. Castranova, X. Shi, J.L. Stauffer, L.M. Demers, F. Chen
• Journal: Oncogene
• Published: 2005;24(31):4873-82
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This laboratory study looked for genes switched on by mineral dust. The authors compared gene activity in lung immune cells called alveolar macrophages, collected by washing the lungs, from non-miners and from coal miners. All volunteers were male nonsmokers. They found a previously uncharacterized gene, which they named mdig. In a follow-up test, mdig was undetectable in cells from all eight normal individuals and highly expressed in cells from four of 11 miners. In a lung cancer cell line (A549), silica particles raised mdig messenger RNA (mRNA) levels about 2.5-fold after 18 hours. Most of seven human lung cancer samples expressed mdig. Nearby noncancerous tissue was available for five of them. In that tissue mdig was barely detectable, except in normal tissue next to one mesothelioma sample. Fifteen of 19 lung cancer cell lines expressed mdig. Blocking mdig in A549 cells slowed their growth and made them more sensitive to damage from silica. Asbestos itself was not tested. The authors concluded that mdig may be involved in regulating cell growth and possibly in the development of cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (molecular biology) study using human lung cells collected by bronchoalveolar lavage, surgical lung cancer tissue samples, and cultured lung cancer cell lines
• Who was studied: Alveolar macrophages came from male nonsmoking volunteers with normal lung function. The initial screen used pooled cells from 3 normal individuals and 3 coal miners. Confirmation used cells from 8 normal individuals and 11 miners. Table 2 lists 35 male controls, 11 male active miners and 11 male inactive miners. The study also used 7 human lung cancer samples from surgery patients and 19 human lung cancer cell lines. The article does not say where or when the volunteers were recruited.
• Exposure: Two exposures were studied. One was coal mine dust, in miners described as having a history of frequent mineral dust exposure. The other was silica particles applied to A549 lung cancer cells in culture (100 mg/ml for 18 h as printed, plus a range of concentrations). No asbestos fibers were tested.
• Main results:
  • In the initial screen of pooled alveolar macrophages, several gene-activity bands appeared only in the cells from miners. One of them (clone 3) matched no known gene and was named mdig.
  • mdig was undetectable in alveolar macrophages from all eight normal individuals. It was highly expressed in those from four of the 11 miners, at different levels of intensity.
  • In A549 lung cancer cells, silica at 100 mg/ml (as printed) for 18 h gave about a 2.5-fold induction of mdig mRNA, measured by semiquantitative RT–PCR. The induction was dose-dependent, peaking at 100–200 mg/ml of silica.
  • Most of the seven human lung cancer samples expressed mdig. Noncancerous surrounding tissue was available for five of the seven (not for samples 11 and 12). In those five, mdig was barely detectable, except in the normal tissue adjacent to the mesothelioma (sample 10).
  • 15 of 19 human lung cancer cell lines expressed mdig under basal conditions. Two lines (H441 and H2347) also expressed a shorter, alternatively spliced version.
  • In normal human tissues, mdig mRNA was detected in liver, skeletal muscle, heart, pancreas and placenta. It was undetectable in brain, lung and kidney.
  • Silencing mdig in A549 cells significantly inhibited cell proliferation compared with a control siRNA. It also delayed the cell cycle transition from G1 to S phase and substantially increased silica-induced LDH release (a measure of cell damage).
• The authors' conclusion: The authors concluded that mdig may be involved in the regulation of cell growth and possibly the development of cancer. They wrote that its overexpression in lung cancers and its role in cell proliferation indicate it may be associated with carcinogenesis.
• Limitations the authors state:
  • More human alveolar macrophage samples were hard to obtain, so further work was done in lung cancer cell lines rather than in human macrophages.
  • The function of the mdig gene had not been fully worked out.
  • The function of the alternatively spliced mdig transcripts was left for future studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Occupational Exposure, Inflammation, Fibrosis, Alveolar Macrophage, A549 Cells.

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