Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma

Our plain-English summary of Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma, by V.J. Amatya, A.S. Mawas, K. Kushitani, et al (International Journal of Oncology, 2016).

The study

• Authors: V.J. Amatya, A.S. Mawas, K. Kushitani, M.M. Mohi El-Din, Y. Takeshima
• Journal: International Journal of Oncology
• Published: 2016;48(4):1599-607
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is a highly aggressive cancer with poor prognosis and refractory to currently available therapies. Most of the patients with advanced invasive nature are not amenable to surgical resection and/or available anticancer therapy, thus development of novel effective therapeutic regimes is needed. Aberrant expression of microRNAs (miRNAs) has been proposed to contribute to carcinogenesis and aggressiveness of mesothelioma. We analyzed miRNA expression in mesothelioma cell lines using TaqMan miRNA expression array and found significant number of miRNAs, which showed increased or lost expression. We validated the increased expression of miR-182, and miR-183 in mesothelioma cell lines by individual miRNA assays and SmartFlare miRNA probes. We further investigated the miR-1, and miR-214, which were not expressed in mesothelioma cells by real-time RT-PCR. Transfection of mesothelioma cells, ACC-Meso-1 and CRL5915, with miRNA mimic (hsa-miR-1 mimic and hsa-miR-214 mimic) led to inhibition of cell growth, invasion and migration. We paid attention to PIM1, the target gene of both miR-1 and miR-214 miRNAs and which was found overexpressed in mesothelioma cells, and miR-1 and miR-214 mimic transfection of mesothelioma cell lines showed downregulation of PIM1 by western blot analysis. The miRNAs, miR-1 and miR-214, may play a role in carcinogenesis of mesothelioma thus might be considered as candidate therapeutic targets in mesothelioma.

In plain English

This laboratory study used mesothelioma cell lines grown in dishes; it did not study mesothelioma patients or their outcomes. The authors measured 754 microRNAs (small molecules that help control genes) in seven mesothelioma cell lines. They compared them with non-cancerous pleural tissue (the lining around the lungs) taken at autopsy from people who died of causes other than cancer. They found 18 microRNAs at higher levels and 20 at reduced or absent levels in the mesothelioma cell lines. Two of the missing ones, miR-1 and miR-214, were added as lab-made copies to two cell lines, ACC-Meso-1 and CRL-5915. Compared with a control, this significantly reduced cell growth at 48 and 72 hours and the number of cells invading through a gel. Treated cells moved more slowly. PIM1, a protein predicted to be targeted by both microRNAs, was highly expressed in all seven cell lines and fell after the treatment. The authors concluded that miR-1 and miR-214 may be attractive targets for future mesothelioma treatment studies. They said studies of human tissue are still needed. The study did not look at asbestos exposure.

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 (in vitro) study of mesothelioma cell lines, compared with non-cancerous human pleural tissue obtained at autopsy, followed by experiments adding microRNA copies to cells; no mesothelioma patients or outcomes were studied
• Who was studied: Seven mesothelioma cell lines: five from the American Type Culture Collection (CRL-2081, -5820, -5826, -5915, -5946) and two from RIKEN, Japan (ACC-Meso-1, ACC-Meso-4). The comparison was non-neoplastic mesothelial cells from the pleura of autopsied patients who died of non-cancer causes. The number of autopsy donors is not stated.
• Exposure: No asbestos exposure was studied. The experimental treatment was transfection of two mesothelioma cell lines with lab-made copies (mimics) of miR-1 and miR-214, compared with a negative control mimic.
• Main results:
  • Out of 754 microRNAs analyzed, 18 had increased expression and 20 had reduced or absent expression in the seven mesothelioma cell lines compared with non-neoplastic mesothelial tissue.
  • Live-cell probes showed increased miR-182 and miR-183 in all seven mesothelioma cell lines.
  • In the two transfected cell lines, miR-1 and miR-214 mimics significantly reduced cell growth compared with the negative control at 48 and 72 hours (p less than 0.05).
  • Treated cells showed significantly fewer cells in the S and G2/M phases of the cell cycle (the phases in which cells copy their DNA and divide) than control cells.
  • Treated cells migrated more slowly in a scratch test than control cells.
  • Fewer treated cells invaded through a gel barrier (p less than 0.05).
  • PIM1, a predicted target of both microRNAs, was highly expressed in all seven mesothelioma cell lines.
  • Cells treated with miR-1 and miR-214 mimics showed reduced PIM1 protein compared with the control mimic.
• The authors' conclusion: The authors concluded that miR-1 and miR-214 may be attractive targets for future mesothelioma treatment studies.
• Limitations the authors state:
  • The authors stated that microRNA expression still needs to be analyzed in human mesothelioma tissue and in reactive (non-cancerous) mesothelial tissue.
  • The authors stated that the use and treatment potential of PIM inhibitors in mesothelioma needs more investigation.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Prognosis, Surgical Resection, Carcinogenesis.

Related studies

• PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells — A.S. Mawas, V.J. Amatya, et al. (2017)
• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)
• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)
• Young investigator challenge: MicroRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology — R. Cappellesso, L. Nicolè, et al. (2016)
• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)

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