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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2014 ; 18
(6
): 991-1003
Nephropedia Template TP
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Analysing the relationship between lncRNA and protein-coding gene and the role of
lncRNA as ceRNA in pulmonary fibrosis
#MMPMID24702795
Song X
; Cao G
; Jing L
; Lin S
; Wang X
; Zhang J
; Wang M
; Liu W
; Lv C
J Cell Mol Med
2014[Jun]; 18
(6
): 991-1003
PMID24702795
show ga
Long non-coding RNAs (lncRNAs) are involved in various pathophysiologic processes
and human diseases. However, their dynamics and corresponding functions in
pulmonary fibrosis remain poorly understood. In this study, portions of lncRNAs
adjacent or homologous to protein-coding genes were determined by searching the
UCSC genome bioinformatics database. This was found to be potentially useful for
exploring lncRNA functions in disease progression. Previous studies showed that
competing endogenous RNA (ceRNA) hypothesis is another method to predict lncRNA
function. However, little is known about the function of ceRNA in pulmonary
fibrosis. In this study, we selected two differentially expressed lncRNAs
MRAK088388 and MRAK081523 to explore their regulatory mechanisms. MRAK088388 and
MRAK081523 were analysed as long-intergenic non-coding RNAs (lincRNAs), and
identified as orthologues of mouse lncRNAs AK088388 and AK081523, respectively.
qRT-PCR and in situ hybridization (ISH) showed that they were significantly
up-regulated, and located in the cytoplasm of interstitial lung cells. We also
showed that MRAK088388 and N4bp2 had the same miRNA response elements (MREs) for
miR-200, miR-429, miR-29, and miR-30, whereas MRAK081523 and Plxna4 had the same
MREs for miR-218, miR-141, miR-98, and let-7. Moreover, the expression levels of
N4bp2 and Plxna4 significantly increased in fibrotic rats, and were highly
correlated with those of MRAK088388 and MRAK081523, respectively. Among their
shared miRNAs, miR-29b-3p and let-7i-5p decreased in the model group, and were
negatively correlated with the expression of MRAK088388 and MRAK081523,
respectively. MRAK088388 and MRAK081523 could regulate N4bp2 and Plxna4
expression by sponging miR-29b-3p and let-7i-5p, respectively, and possessed
regulatory functions as ceRNAs. Thus, our study may provide insights into the
functional interactions of lncRNA, miRNA and mRNA, and lead to new theories for
the pathogenesis and treatment of pulmonary fibrosis.