Overexpression of microRNA‑486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1

Our plain-English summary of Overexpression of microRNA‑486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1, by S. Pinelli, R. Alinovi, D. Poli, et al (International Journal of Molecular Medicine, 2021).

The study

• Authors: S. Pinelli, R. Alinovi, D. Poli, M. Corradi, G. Pelosi, M. Tiseo, M. Goldoni, D. Cavallo, P. Mozzoni
• Journal: International Journal of Molecular Medicine
• Published: 2021;47(6)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Dysregulated levels of microRNAs (miRNAs or miRs), involved in oncogenic pathways, have been proposed to contribute to the aggressiveness of malignant pleural mesothelioma (MPM). Previous studies have highlighted the downregulation of miRNA miR‑486‑5p in patients with mesothelioma and the introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important therapeutic strategy. The aim of the present study was to evaluate the mechanisms through which miRNAs may influence the functions, proliferation and sensitivity to cisplatin of MPM cells. In the present study, a miR‑486‑5p mimic was transfected into the H2052 and H28 MPM cell lines, and cell viability, proliferation, apoptosis and mitochondrial membrane potential were monitored. miR‑486‑5p overexpression led to a clear impairment of cell proliferation, targeting CDK4 and attenuating cell cycle progression. In addition, transfection with miR‑486‑5p mimic negatively regulated the release of inflammatory factors and the expression of Provirus integration site for Moloney murine leukaemia virus 1 (PIM1). The sensitivity of the cells to cisplatin was enhanced by enhancing the apoptotic effects of the drug and impairing mitochondrial function. On the whole, the present study demonstrates that miR‑486‑5p may play an important role in MPM treatment by targeting multiple pathways involved in tumour development and progression. These activities may be mostly related to the downregulation of PIM1, a crucial regulator of cell survival and proliferation. Furthermore, these results provide support for the combined use of miR‑486‑5p with chemotherapy as a therapeutic strategy for MPM.

In plain English

This was a laboratory study of two human malignant pleural mesothelioma cell lines, H28 and H2052, grown in culture. No patients and no asbestos fibers were studied. The authors raised the level of a small regulatory molecule, microRNA-486, in the cells by adding a synthetic copy (a 'mimic'). They then tested the cells with and without the chemotherapy drug cisplatin. Raising microRNA-486 slowed the growth of both cell lines from 48 hours on, without significant cell death. More cells were held at an early stage of the cell-division cycle. Levels of the cell-cycle regulators CDK4, cyclin D1 and cyclin E1 fell, as did the survival protein PIM1. Release of the inflammatory molecule IL-6 fell by about 30% compared with controls. With cisplatin alone, the concentration that cut cell viability in half at 48 hours was 17.83 µM for H2052 cells and 50 µM for H28 cells. Cells given microRNA-486 survived cisplatin less well than cells given the drug alone, and more of them died by apoptosis. The authors concluded that combining cisplatin with microRNA-486 may offer a potential therapeutic advantage in mesothelioma.

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) experiment on human mesothelioma cell lines, using transfection with a microRNA-486 mimic, with and without cisplatin treatment
• Who was studied: Two human malignant pleural mesothelioma cell lines, H28 and H2052, obtained from the American Type Culture Collection; no human participants
• Exposure: Transfection with a microRNA-486 mimic (10 or 50 nM; 10 nM used in later experiments) and treatment with cisplatin (CDDP) at 0 to 100 µM for 24, 48 or 72 hours. Asbestos exposure was not studied.
• Main results:
  • In both cell lines, microRNA-486 was overexpressed compared with controls after transfection, with no significant difference between the 10 nM and 50 nM concentrations
  • MicroRNA-486 overexpression reduced proliferation of both cell lines without significant lysis or apoptosis; the decrease appeared at 48 hours and was time-dependent
  • Transfected cells showed a higher percentage of cells arrested in the G0/G1 phase of the cell cycle
  • Expression of CCNE1, CCND1 and CDK4 decreased significantly in transfected H28 and H2052 cells, at different time points and to varying extents
  • PIM1 expression decreased over time from 24 hours, reaching maximum significance at 72 hours compared with the untreated control
  • Release of IL-6 into the culture medium decreased by approximately 30% compared with controls
  • With cisplatin alone, the IC50 at 48 hours was 17.83 µM for H2052 cells and 50 µM for H28 cells
  • In both cell lines, microRNA-486 reduced viability from 48 hours of cisplatin exposure compared with cells treated with the drug alone
  • The combination increased the number of apoptotic cells and stimulated caspase-3 activity
  • Adding cisplatin to microRNA-486 did not further decrease PIM1 expression compared with the mimic alone
  • The increase in intracellular reactive oxygen species was significant in H2052 cells given microRNA-486 plus cisplatin; in H28 cells it was lower and not significant compared with the control
• The authors' conclusion: The authors concluded that microRNA-486 enhanced the inhibitory and apoptotic effects of cisplatin, suggesting a potential therapeutic advantage of combined cisplatin and microRNA-486 treatment in human malignant pleural mesothelioma

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, Pleural Mesothelioma, Cisplatin, Apoptosis, Chemotherapy.

Related studies

• Differential microRNA expression profiling of mesothelioma and expression analysis of miR-1 and miR-214 in mesothelioma — V.J. Amatya, A.S. Mawas, et al. (2016)
• PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells — A.S. Mawas, V.J. Amatya, et al. (2017)
• Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration — W. Blum, L. Pecze, et al. (2015)
• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)
• A subset of microRNAs defining the side population of a human malignant mesothelioma cell line — M.C. Kim, N.Y. Kim, et al. (2017)
• MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma — M. Tomasetti, F. Monaco, et al. (2016)

Browse more research in International Journal of Molecular Medicine, or return to medical research.