#0138 MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck
Unraveling the Molecular Mechanism of Asbestos-Induced Lung Cancer
Asbestos is a naturally occurring fibrous mineral with attractive properties, such as resistance to heat, electricity, and corrosion, that make it useful as an insulator in a variety of industrial applications. However, if inhaled, asbestos fibers can become trapped in the lungs, and lead to the development of lung cancer and malignant mesothelioma, a cancer of the tissue lining surrounding the lung.
Several pathways for asbestos-induced lung cancer have been proposed, including variations in the expression of microRNA (miRNA), a non-coding RNA that plays a critical roles in regulating gene expression and contributes to diseases, including cancer. While considered a possible biomarker of asbestos-induced cancers, the precise role of miRNA in lung cancer remains unclear.
In a new study, a team of researchers from Japan looked at the expression levels of miRNA and possible target genes in the lung tissues of mice models exposed to asbestos. They administered chrysotile, or white asbestos, and crocidolite, or blue asbestos, directly into the trachea (windpipe) of male mice models four times weekly. They then extracted RNA from their lung tissues and conducted microarray and database analyses. Additionally, the team also performed real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry to verify the results of microarray analysis.
They found that exposure to chrysotile and crocidolite markedly altered the levels of 14 miRNAs. In particular, it greatly increased the levels of miR-21, a tumor-inducing miRNA. The database analysis revealed that miR-21 targets and inhibits tumor-suppressing genes, such as programmed cell death 4 (PDCD4) and reversion inducing-cysteine-rich protein with kazal motifs (Reck).
Interestingly, real-time PCR did not reveal any significant reduction in PDCD4 expression from asbestos exposure. However, both Western blotting and immunohistochemistry analyses showed that chrysotile lowered PDCD4 expression. In addition, chrysotile also reduced the expression of Reck, as revealed by PCR and immunohistochemistry analyses.
The team believes that these molecular events constitute an early response to asbestos exposure, and, in turn, an early warning sign for lung toxicity and lung cancer. While further studies are necessary to determine whether miRNAs and their target genes can serve as biomarkers for asbestos-induced diseases, the team’s findings are the first to highlight the role of miR-21 in the development of asbestos-induced lung cancer.
Link to original journal article:
https://academic.oup.com/joh/article/63/1/e12282/7249815
Title of the paper:
MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck
Authors:
Yusuke Hiraku, Jun Watanabe, Akira Kaneko, Takamichi Ichinose, and Mariko Murata
