Downregulation of lncRNA PVT1 inhibits proliferation and migration of mesothelioma cells by targeting FOXM1

Our plain-English summary of Downregulation of lncRNA PVT1 inhibits proliferation and migration of mesothelioma cells by targeting FOXM1, by Y. Fujii, V.J. Amatya, K. Kushitani, et al (Oncology Reports, 2022).

The study

• Authors: Y. Fujii, V.J. Amatya, K. Kushitani, R. Suzuki, Y. Kai, T. Kambara, Y. Takeshima
• Journal: Oncology Reports
• Published: 2022;47(2)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a highly aggressive tumor, and an effective strategy for its treatment is not yet available. Long non‑coding RNAs (lncRNAs) have been reported to be associated with various biological processes, including the regulation of gene expression of cancer‑related pathways. Among various lncRNAs, plasmacytoma variant translocation 1 (PVT1) acts as a tumor promoter in several human cancers, but its mechanism of action has not yet been elucidated. Increased PVT1 expression was identified in ACC‑MESO‑1, ACC‑MESO‑4, CRL‑5915, and CRL‑5946 mesothelioma cell lines. PVT1 expression was investigated in mesothelioma cell lines by reverse transcription‑quantitative polymerase chain reaction and its functional analysis by cell proliferation, cell cycle, cell migration, and cell invasion assays, as well as western blot analysis of downstream target genes. Knockdown of PVT1 expression in these cell lines by small interfering RNA transfection resulted in decreased cell proliferation and migration and increased the proportion of cells in the G2/M phase. The results of reverse transcription‑quantitative polymerase chain reaction analysis revealed that PVT1 knockdown in mesothelioma cell lines caused the downregulation of Forkhead box M1 (FOXM1) expression, while the results of western blot analysis revealed that this knockdown reduced FOXM1 expression at the protein level. In addition, combined knockdown of PVT1 and FOXM1 decreased the proliferation of mesothelioma cell lines. In conclusion, PVT1 and FOXM1 were involved in the proliferation of cancer cells. Therefore, PVT1‑FOXM1 pathways may be considered as candidate targets for the treatment of malignant mesothelioma.

In plain English

This laboratory study, by a pathology group at Hiroshima University in Japan, used four human mesothelioma cell lines grown in dishes (ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946) and two lung adenocarcinoma cell lines. It did not study patients or asbestos exposure. The authors measured a long non-coding RNA called PVT1. They then used small interfering RNA to reduce ("knock down") PVT1, a gene called FOXM1, or both. PVT1 levels in the mesothelioma lines were 1.8 to 2.4 times the average of the lung adenocarcinoma lines. In the mesothelioma lines, knocking down PVT1 for 3 days reduced cell viability by 14.8% to 23.3%, depending on the line. It also raised the share of cells in the G2/M phase of the cell cycle and slowed cell migration, but it was not significantly linked to invasion. PVT1 knockdown lowered FOXM1 at both the RNA and protein levels. Knocking down both genes reduced viability by 29.1% to 39.9%. The authors concluded that PVT1 and FOXM1 may be considered candidate targets for mesothelioma therapy. They noted that spheroid and in vivo experiments are still needed.

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 using gene knockdown by small interfering RNA; experiments repeated at least three times in triplicate
• Who was studied: Four human mesothelioma cell lines (ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946) and two lung adenocarcinoma cell lines (A549 and PC9), studied at the Department of Pathology, Hiroshima University, Japan; no patients were studied
• Exposure: No asbestos exposure was studied. The experimental treatment was small interfering RNA (siRNA) against PVT1, against FOXM1, or both, compared with negative control siRNA
• Main results:
  • Compared with the average of the two lung adenocarcinoma cell lines, PVT1 expression was 1.8-, 1.8-, 2.4- and 1.8-fold higher in ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946, respectively
  • PVT1 siRNA reduced PVT1 expression by more than 80% in all mesothelioma cell lines compared with negative control siRNA
  • After 3 days, PVT1 knockdown significantly reduced viability of ACC-MESO-1 cells by 22.9%, ACC-MESO-4 by 14.8%, CRL-5915 by 17.6% and CRL-5946 by 23.3%
  • The share of cells in the G2/M phase was significantly higher with PVT1 siRNA (28.7, 27.4, 21.0 and 30.3% in ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946) than with control siRNA (17.5, 15.6, 14.4 and 22.8%)
  • PVT1 knockdown reduced migration of ACC-MESO-1 by 67.5% at 24 h, and of ACC-MESO-4, CRL-5915 and CRL-5946 by 64.2, 26.8 and 27.3% at 48 h; PVT1 knockdown was not significantly associated with invasion in any of the four lines (data not shown)
  • PVT1 knockdown lowered FOXM1 RNA by 77, 83, 84 and 82%, and FOXM1 protein by 41, 35, 56 and 55%, in ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946, respectively
  • After 3 days, FOXM1 knockdown alone reduced viability by 24.8, 19.0, 19.2 and 24.4%, and combined PVT1 and FOXM1 knockdown by 37.9, 35.7, 29.1 and 39.9%, in ACC-MESO-1, ACC-MESO-4, CRL-5915 and CRL-5946, respectively
• The authors' conclusion: The authors concluded that PVT1 was upregulated in mesothelioma cell lines, that its knockdown decreased proliferation and migration and downregulated FOXM1, and that PVT1 and FOXM1 may be considered candidate targets for therapy of malignant mesothelioma
• Limitations the authors state:
  • The authors stated that spheroid formation and in vivo experiments were limited in this study and that further such studies are needed to clarify the function of PVT1-FOXM1

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, Translocation.

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