PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells

Our plain-English summary of PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells, by A.S. Mawas, V.J. Amatya, R. Suzuki, et al (International Journal of Oncology, 2017).

The study

• Authors: A.S. Mawas, V.J. Amatya, R. Suzuki, K. Kushitani, M.M. Mohi El-Din, Y. Takeshima
• Journal: International Journal of Oncology
• Published: 2017;50(3):1029-1034
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection. Here, we report that the downregulation of PIM1 led to suppression of cell proliferation by cell cycle arrest at G1 phase and suppression of cell invasion and migration. Considering the mesothelioma as rapidly growing invasive cancer, downregulation of PIM1 may have a potential role for therapeutic management of malignant mesothelioma.

In plain English

This was a laboratory study of mesothelioma cells grown in dishes, not of people, and it did not study asbestos exposure. The authors used small interfering RNA (siRNA) to switch down a gene called PIM1 in two mesothelioma cell lines, CRL-5915 and ACC-MESO-1. They compared these cells with cells given a control siRNA. PIM1 messenger RNA fell by 50 to 70%, and PIM1 protein was also reduced. Cells with lowered PIM1 showed about 20% lower growth over three days. After two days, the share of cells held in the G1 stage of the cell cycle (before cells copy their DNA) was 60.5% in ACC-MESO-1 and 65.8% in CRL-5915, against 43.3% and 50% in control cells. After three days the gap was smaller. Cells with lowered PIM1 were about 30% less able to invade through a gel layer and moved less in a scratch test. The authors concluded that lowering PIM1 has potential for treating mesothelioma. They added that more work is needed on how PIM1 acts on the genes it controls.

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) cell-line experiment: siRNA knockdown of the PIM1 gene compared with a negative-control siRNA
• Who was studied: Two mesothelioma cell lines: CRL-5915 (from the American Type Culture Collection, USA) and ACC-MESO-1 (from RIKEN BioResearch Center, Japan); no human participants
• Exposure: No asbestos exposure was studied. The cells were treated with 20 nM of PIM1-siRNA or negative-control siRNA, in triplicate.
• Main results:
  • In cells given PIM1-siRNA, PIM1 mRNA was reduced by 50 to 70%.
  • PIM1 protein was also reduced, as shown by western blot.
  • In both cell lines, cells given PIM1-siRNA showed about 20% reduced proliferation compared with negative-control siRNA cells over 24, 48 and 72 h (P less than 0.01 in Figure 2).
  • After 2 days, the share of cells in G1 phase with PIM1-siRNA was 60.5% (ACC-MESO-1) and 65.8% (CRL-5915). The table gives P = 0.0001 and P = 0.0009.
  • After 2 days, the matching G1 shares in negative-control cells were 43.3% (ACC-MESO-1) and 50% (CRL-5915).
  • After 3 days, the G1 share was 84% (ACC-MESO-1) and 78.6% (CRL-5915) with PIM1-siRNA, versus 74.5% and 74.1% with negative control. The authors noted that G1 arrest was greater on day 2 than on day 3 in both cell lines.
  • Cells given PIM1-siRNA were about 30% less invasive through Matrigel. Mean invading cells per quadrant: CRL-5915, 1716 (SD 313) versus 2439 (SD 686), P = 0.0168; ACC-MESO-1, 1074 (SD 230) versus 1684 (SD 309), P = 0.0005.
  • In a wound/scratch assay, cells given PIM1-siRNA migrated less than negative-control cells (P less than 0.05 in Figure 5).
• The authors' conclusion: The authors concluded that lowering PIM1 reduced proliferation, invasion and migration of mesothelioma cells and has potential for therapeutic management of mesothelioma.
• Limitations the authors state:
  • The authors stated that further study of how PIM1 regulates its downstream genes is needed to understand how it affects mesothelioma cells.

Topics

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

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

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)
• The Wnt regulator SFRP4 inhibits mesothelioma cell proliferation, migration, and antagonizes Wnt3a via its netrin-like domain — V. Perumal, A.M. Dharmarajan, et al. (2017)
• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)
• Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma — S. Wang, L. Jiang, et al. (2016)
• Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration — W. Blum, L. Pecze, et al. (2015)
• AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma — H. Sudo, A.B. Tsuji, et al. (2014)

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