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Updated: May 6, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma
G Reid1, M E Pel, M B Kirschner
1Asbestos Diseases Research Institute, University of Sydney, Sydney, Australia.
Background:
Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown.
Materials And Methods:
MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies.
Results:
Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth.
Conclusions:
The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.
Insights
MicroRNA-15/16 (miR-15/16) is downregulated in malignant pleural mesothelioma (MPM), acting as a tumor suppressor. Restoring miR-16 expression inhibits MPM growth and sensitizes cells to chemotherapy, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Malignant pleural mesothelioma (MPM) is a challenging cancer with limited treatment options.
- The miR-15/16 microRNA family is implicated as tumor suppressors in various cancers.
- The role of miR-15/16 in MPM has not been well-defined.
Purpose of the Study:
- To investigate the expression status of the miR-15/16 family in MPM.
- To determine the functional role of miR-15/16 in MPM cell proliferation and drug sensitivity.
- To evaluate the therapeutic potential of restoring miR-16 expression in MPM.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to analyze microRNA expression in MPM tissues and cell lines.
- Synthetic microRNA mimics were employed to restore miR-15/16 expression in vitro.
- In vivo studies involved treating MPM xenografts in mice with miR-16 mimics encapsulated in targeted minicells.
Main Results:
- The miR-15 family, including miR-15/16, showed consistent downregulation in MPM tumors and cell lines compared to normal tissues.
- Restoring miR-15/16 expression in MPM cell lines inhibited proliferation and sensitized them to pemetrexed and gemcitabine.
- In vivo administration of miR-16 mimics effectively inhibited MPM tumor growth in a dose-dependent manner.
Conclusions:
- The miR-15/16 family exhibits tumor suppressor activity in malignant pleural mesothelioma.
- Restoring miR-16 expression presents a promising novel therapeutic strategy for MPM treatment.
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