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

藤井 祐太朗 広島大学

2022.03.23

概要

Malignant mesothelioma is a highly aggressive tumor with poor
prognosis. It arises from mesothelial cells lining the serous
cavities (pleura, pericardium, peritoneum and tunica vagi‑
nalis). The incidence of mesothelioma is increasing worldwide
due to previous occupational and/or environmental exposure
to asbestos (1,2). The incidence of malignant mesothelioma in
Japan is predicted to reach a peak between 2030 and 2034. In
developing countries, the incidence of this disease is predicted
to increase due to the continued use of asbestos (3,4). Currently
available treatments have a limited effect on malignant meso‑
thelioma management (5). Therefore, there is a need to identify
feasible and effective therapeutic targets.
Non‑coding RNAs are RNA molecules that are transcribed
from the genome but do not encode proteins. They have
been revealed to play structural and functional roles within
the cell (6‑10). They are primarily grouped into two classes
based on transcript size: Small non‑coding RNAs and long
non‑coding RNAs (lncRNAs) (11). Small non‑coding RNAs
include microRNAs (miRNAs) that function as major regula‑
tors of gene expression and complex components of cellular
gene expression networks. In contrast to miRNAs, lncRNAs
are a class of RNA transcripts that are over 200 nucleotides
in length (12). lncRNAs have been associated with various
biological processes, including epigenetics, alternative
splicing, and nuclear import; additionally, they function as
precursors of small non‑coding RNAs, and regulators of
mRNA decay (13‑15). Dysregulated lncRNA expression has
been reported in numerous cancers, suggesting that lncRNAs
are a newly emerging class of oncogenic and tumor‑suppressor
genes (16).
Plasmacytoma variant translocation 1 (PVT1) is an onco‑
genic lncRNA located at chromosomal region 8q24 (17). The
carcinogenicity of PVT1 has been identified in various human
cancers, including non‑small cell lung (18), leukemia (19),
hepatocellular (20), colon (21), breast (22), and ovarian
cancer (23). Non‑coding RNA expression data from Human
Transcriptome 2.0 GeneChip Array analysis performed in
our previous study revealed increased PVT1 expression in
epithelioid mesothelioma and lung adenocarcinoma (24). In
the present study, the biological function of PVT1 in mesothe‑
lioma was elucidated. ...

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