CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis

Our plain-English summary of CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis, by M. Guled, L. Lahti, P.M. Lindholm, et al (Genes, Chromosomes & Cancer, 2009).

The study

• Authors: M. Guled, L. Lahti, P.M. Lindholm, K. Salmenkivi, I. Bagwan, A.G. Nicholson, S. Knuutila
• Journal: Genes, Chromosomes & Cancer
• Published: 2009;48(7):615-23
• Cited by: 223 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial cells, mainly due to former asbestos exposure. Little is known about the microRNA (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an essential role in the regulation of gene expression. This study was carried out to analyze the miRNA expression profile of 17 MM samples using miRNA microarray. The analysis distinguished the overall miRNA expression profiles of tumor tissue and normal mesothelium. Differentially expressed miRNAs were found in tumor samples compared with normal sample. Twelve of them, let-7b*, miR-1228*, miR-195*, miR-30b*, miR-32*, miR-345, miR-483-3p, miR-584, miR-595, miR-615-3p, and miR-885-3p, were highly expressed whereas the remaining nine, let-7e*, miR-144*, miR-203, miR-340*, miR-34a*, miR-423, miR-582, miR-7-1*, and miR-9, were unexpressed or had severely reduced expression levels. Target genes for these miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN, HGF, and PDGFA. Many of the miRNAs were located in chromosomal areas known to be deleted or gained in MM such as 8q24, 1p36, and 14q32. Furthermore, we could identify specific miRNAs for each histopathological subtype of MM. Regarding risk factors such as smoking status and asbestos exposure, significantly differentially expressed miRNAs were identified in smokers versus nonsmokers (miR-379, miR-301a, miR-299-3p, miR-455-3p, and miR-127-3p), but not in asbestos-exposed patients versus nonexposed ones. This could be related to the method of assessment of asbestos exposure as asbestos remains to be the main contributor to the development of MM.

In plain English

This laboratory study used a microarray to measure microRNAs, small molecules that help control which genes are active, in 17 frozen tumor samples from patients with malignant mesothelioma. The authors compared them with one commercial sample of total RNA from normal human pericardium. The control sample showed 333 microRNAs and the tumor samples showed 152. Twelve microRNAs appeared only in tumors, while nine were detected in the control but in no tumor sample; other control microRNAs appeared in some tumors only. In all, the authors identified 21 microRNAs that differed in the tumors. Using computer prediction databases, they linked some to genes often affected in mesothelioma, including CDKN2A, NF2 and JUN. Each tumor subtype had its own specific microRNAs, although the sarcomatoid subtype was a single sample. Tumors from smokers, including former smokers, differed from nonsmokers' tumors. No significant differences were found between patients with and without asbestos exposure (q greater than 0.85), nor in survival by exposure. The authors noted that exposure was based on patients' own knowledge. The authors concluded that microRNA expression distinguished tumor from normal tissue and revealed subtype-specific microRNAs.

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 study (miRNA microarray analysis) of tumor tissue samples compared with a commercial total RNA control from normal human pericardium
• Who was studied: 17 fresh frozen malignant mesothelioma samples from patients at the Royal Brompton and Harefield NHS Trust (UK), chosen on the basis of tumor content (30 to 90%). There were 11 epithelioid (including one deciduoid variant), 5 biphasic and 1 sarcomatoid. Operation dates in the clinical table run from 2000 to 2005.
• Exposure: Asbestos exposure was recorded only as yes or no, based on the patient's own knowledge. No fiber types, products, jobs or doses are given. Smoking status (smokers including former smokers, versus nonsmokers) was also compared.
• Main results:
  • In the normal control sample, 333 of 723 human miRNAs were detected; 140 of these were also detected in the tumor samples.
  • 12 miRNAs were detected only in the tumor samples, bringing the total detected in tumors to 152.
  • Some miRNAs detected in the control were also detected in some individual tumor samples but not others.
  • Nine miRNAs were detected in the control sample and in none of the tumor samples.
  • In total, 21 miRNAs were identified as differentially expressed in the tumor samples.
  • Computer-based target prediction (Sanger miRBase, miRanda) linked these miRNAs to genes known in mesothelioma. JUN was a predicted target of two down-regulated miRNAs, miR-9 and miR-203. CDKN2A and NF2 were predicted targets of miR-885-3p.
  • Some miRNAs were found only in one subtype: seven for epithelioid, five for biphasic and three for sarcomatoid. Epithelioid and biphasic profiles were the most closely correlated.
  • No significant differences in miRNA expression were seen between tumors from asbestos-exposed and nonexposed patients (q greater than 0.85).
  • Smokers (including former smokers) versus nonsmokers showed differentially expressed miRNAs. The most differentially expressed (P less than 0.0005; q less than 0.05) were listed as miR-379, miR-301a, miR-299-3p and miR-455-3p.
  • Survival was compared between asbestos-exposed and nonexposed patients, and no significant differences were detected; the data were not shown.
• The authors' conclusion: The authors concluded that miRNA expression distinguished mesothelioma tumor tissue from normal tissue and revealed specific miRNAs for the histopathological subtypes.
• Limitations the authors state:
  • Asbestos exposure was based on the patient's own knowledge, and some patients classed as nonexposed may not have known of a past exposure.
  • The sarcomatoid subtype was represented by only one sample, so its results are preliminary.
  • Larger sample sets are needed to detect significant survival differences.
  • The single deciduoid case had the lowest tumor content and no replicate measurement.

Topics

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

Medical terms in this study, explained in our Lexicon: CDKN2A, Malignant Mesothelioma, Mesothelial Cells, Asbestos Exposure, Mesothelium.

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