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2016 ; 7
(10
): 11696-707
Nephropedia Template TP
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Long non-coding RNA LINC01133 represses KLF2, P21 and E-cadherin transcription
through binding with EZH2, LSD1 in non small cell lung cancer
#MMPMID26840083
Zang C
; Nie FQ
; Wang Q
; Sun M
; Li W
; He J
; Zhang M
; Lu KH
Oncotarget
2016[Mar]; 7
(10
): 11696-707
PMID26840083
show ga
Long non-coding RNAs are emerging as crucial regulators and prognostic markers in
multiple cancers including non small cell lung cancer (NSCLC). In this study, we
screened LINCO1133 as a new candidate lncRNA which promotes NSCLC development and
progression, in two independent datasets (GSE18842 and GSE19804) from the Gene
Expression Omnibus (GEO). LINC01133 is previously found to be over-expressed in
lung squamous cell cancer (LSCC) and knockdown its expression inhibits LSCC cells
invasion. However, its' molecular mechanism and downstream targets involving in
regulation of cancer cells phenotype is not known. Here, we found that LINC01133
expression is up-regulated in NSCLC tissues, and its' over-expression is
associated with patients poor prognosis and short survival time. LINC01133
knockdown decreased NSCLC cells proliferation, migration, invasion and induced
cell cycle G1/S phase arrest and cell apoptosis. Mechanistic investigations
showed that LINC01133 could interact with EZH2, LSD1 and recruit them to KLF2,
P21 or E-cadherin promoter regions to repress their transcription. Furthermore,
rescue experiments demonstrated that LINC01133 oncogenic function is partly
through regulating KLF2. Lastly, we found that there was negative correlation
between LINC01133 and KLF2, P21 or E-cadherin in NSCLC. Overall, our findings
illuminate how LINC01133 over-expression confers an oncogenic function in NSCLC
that may offer a novel therapy target in this disease.