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A novel lnc-PCF promotes the proliferation of TGF-?1-activated epithelial cells
by targeting miR-344a-5p to regulate map3k11 in pulmonary fibrosis
#MMPMID29072702
Liu H
; Wang B
; Zhang J
; Zhang S
; Wang Y
; Zhang J
; Lv C
; Song X
Cell Death Dis
2017[Oct]; 8
(10
): e3137
PMID29072702
show ga
Emerging evidence suggests that microRNA (miRNA) and long noncoding RNA (lncRNA)
play important roles in disease development. However, the mechanism underlying
mRNA interaction with miRNA and lncRNA in idiopathic pulmonary fibrosis (IPF)
remains unknown. This study presents a novel lnc-PCF that promotes the
proliferation of TGF-?1-activated epithelial cells through the regulation of
map3k11 by directly targeting miR-344a-5p during pulmonary fibrogenesis.
Bioinformatics and in vitro translation assay were performed to confirm whether
or not lnc-PCF is an actual lncRNA. RNA fluorescent in situ hybridization (FISH)
and nucleocytoplasmic separation showed that lnc-PCF is mainly expressed in the
cytoplasm. Knockdown and knockin of lnc-PCF indicated that lnc-PCF could promote
fibrogenesis by regulating the proliferation of epithelial cells activated by
TGF-?1 according to the results of xCELLigence real-time cell analysis system,
flow cytometry, and western blot analysis. Computational analysis and a
dual-luciferase reporter system were used to identify the target gene of
miR-344a-5p, whereas RNA pull down, anti-AGO2 RNA immunoprecipitation, and rescue
experiments were conducted to confirm the identity of this direct target. Further
experiments verified that lnc-PCF promotes the proliferation of activated
epithelial cells that were dependent on miR-344a-5p, which exerted its regulatory
functions through its target gene map3k11. Finally, adenovirus packaging
sh-lnc-PCF was sprayed into rat lung tissues to evaluate the therapeutic effect
of lnc-PCF. These findings revealed that lnc-PCF can accelerate pulmonary
fibrogenesis by directly targeting miR-344a-5p to regulate map3k11, which may be
a potential therapeutic target in IPF.
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