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2016 ; 8
(9
): 1052-64
Nephropedia Template TP
gab.com Text
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English Wikipedia
LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated
in aggressive breast cancer
#MMPMID27485121
Sas-Chen A
; Aure MR
; Leibovich L
; Carvalho S
; Enuka Y
; Körner C
; Polycarpou-Schwarz M
; Lavi S
; Nevo N
; Kuznetsov Y
; Yuan J
; Azuaje F
; Ulitsky I
; Diederichs S
; Wiemann S
; Yakhini Z
; Kristensen VN
; Børresen-Dale AL
; Yarden Y
EMBO Mol Med
2016[Sep]; 8
(9
): 1052-64
PMID27485121
show ga
Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in
pathogenesis, including cancer. Recently, lncRNAs have been implicated in
progression of specific subtypes of breast cancer. One aggressive, basal-like
subtype associates with increased EGFR signaling, while another, the
HER2-enriched subtype, engages a kin of EGFR Based on the premise that
EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we
identified multiple EGFR-inducible lncRNAs in basal-like normal cells and
overlaid them with the transcriptomes of over 3,000 breast cancer patients. This
led to the identification of 11 prognostic lncRNAs. Functional analyses of this
group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a
highly conserved lncRNA, which is depleted in basal-like and in HER2-positive
tumors, and the low expression of which predicts poor patient prognosis.
Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone
deacetylation at the respective promoter. We also find that LIMT inhibits
extracellular matrix invasion of mammary cells in vitro and tumor metastasis
in vivo In conclusion, lncRNAs dynamically regulated by growth factors might act
as novel drivers of cancer progression and serve as prognostic biomarkers.