MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p

Our plain-English summary of MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p, by P. Wang, C. Bai, S. Shen, et al (Open Medicine, 2021).

The study

• Authors: P. Wang, C. Bai, S. Shen, C. Jiang, J. Deng, D. Han
• Journal: Open Medicine
• Published: 2021;16(1):1653-1667
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual-luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

© 2021 Pei Wang et al., published by De Gruyter.

In plain English

This was a laboratory study using cell lines and mice. It did not study asbestos exposure or people. The authors compared three malignant pleural mesothelioma (MPM) cell lines (NCI-H226, NCI-H2452 and MSTO-211H) with a normal mesothelial cell line (Met-5A). They measured a gene product called MALAT1 and a small RNA called miR-141-3p. MALAT1 levels were reported as significantly higher, and miR-141-3p levels as lower, in the MPM cell lines. When MALAT1 was reduced, the cells grew, migrated and invaded less, more died, and more stopped in the G0/G1 cell-cycle phase. Mice injected with MALAT1-reduced NCI-H226 cells had significantly smaller tumors than control mice. Further tests indicated that MALAT1 binds miR-141-3p, and that miR-141-3p in turn lowers a protein called YAP1. In H226 and H2452 cells, blocking miR-141-3p reversed the falls in YAP1 and TEAD1 levels, growth and invasion, and the rise in cell death, that followed reducing MALAT1. The authors concluded that MALAT1 may promote mesothelioma development by binding miR-141-3p and so acting through YAP1. Results were reported mainly as figures and p-values.

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 experiments on human cell lines, plus an animal experiment in which tumor cells were transplanted into mice (6 mice per group according to the methods)
• Who was studied: One normal mesothelial cell line (Met-5A) and three MPM cell lines (NCI-H226, NCI-H2452, MSTO-211H) purchased from a Chinese cell bank; female BALB/C nude mice transplanted with NCI-H226 cells
• Exposure: No asbestos exposure was studied. The experimental interventions were genetic: reducing MALAT1 (sh-MALAT1), adding or blocking miR-141-3p (mimics and inhibitor), and reducing YAP1 (si-YAP1), each compared with negative controls
• Main results:
  • MALAT1 levels were significantly higher in the MPM cell lines than in the normal Met-5A cell line, especially in NCI-H226 and NCI-H2452
  • In H226 and H2452 cells, reducing MALAT1 lowered proliferation, migration and invasion, increased apoptosis (cell death), and increased the proportion of cells in the G0/G1 phase
  • Mice given MALAT1-reduced NCI-H226 cells had significantly smaller tumors than the control (sh-NC) group
  • miR-141-3p levels were lower in the three MPM cell lines than in Met-5A cells
  • In a reporter test, miR-141-3p mimics significantly reduced the signal from the normal (wild-type) MALAT1 binding site but not from the mutated site, which the authors took as evidence of direct binding
  • Increasing miR-141-3p in MPM cells reduced proliferation, migration and invasion, and induced apoptosis
  • Both reducing MALAT1 and increasing miR-141-3p lowered YAP1 and TEAD1 protein levels in MPM cells
  • In rescue experiments on H226 and H2452 cells, a miR-141-3p inhibitor reversed the drop in YAP1 and TEAD1 caused by reducing MALAT1. It also reversed the reported changes in proliferation, apoptosis and invasion. Rescue of migration, cell-cycle changes or mouse tumor growth was not reported.
• The authors' conclusion: The authors concluded that MALAT1 acts as a competitive endogenous RNA (ceRNA) that binds miR-141-3p and may promote MPM development by targeting YAP1. They suggested it as a possible treatment target.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Metastasis, Lung Adenocarcinoma, Apoptosis, Hippo Signaling Pathway.

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