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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+Biol+Chem
2017 ; 292
(30
): 12483-12495
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A new long noncoding RNA (lncRNA) is induced in cutaneous squamous cell carcinoma
and down-regulates several anticancer and cell differentiation genes in mouse
#MMPMID28596382
Ponzio G
; Rezzonico R
; Bourget I
; Allan R
; Nottet N
; Popa A
; Magnone V
; Rios G
; Mari B
; Barbry P
J Biol Chem
2017[Jul]; 292
(30
): 12483-12495
PMID28596382
show ga
Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common
metastatic skin cancer. Although some of the early events involved in this
pathology have been identified, the subsequent steps leading to tumor development
are poorly defined. We demonstrate here that the development of mouse tumors
induced by the concomitant application of a carcinogen and a tumor promoter
(7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate
(TPA), respectively) is associated with the up-regulation of a previously
uncharacterized long noncoding RNA (lncRNA), termed AK144841. We found that
AK144841 expression was absent from normal skin and was specifically stimulated
in tumors and highly tumorigenic cells. We also found that AK144841 exists in two
variants, one consisting of a large 2-kb transcript composed of four exons and
one consisting of a 1.8-kb transcript lacking the second exon. Gain- and
loss-of-function studies indicated that AK144841 mainly inhibited gene
expression, specifically down-regulating the expression of genes of the late
cornified envelope-1 (Lce1) family involved in epidermal terminal differentiation
and of anticancer genes such as Cgref1, Brsk1, Basp1, Dusp5, Btg2, Anpep, Dhrs9,
Stfa2, Tpm1, SerpinB2, Cpa4, Crct1, Cryab, Il24, Csf2, and Rgs16 Interestingly,
the lack of the second exon significantly decreased AK144841's inhibitory effect
on gene expression. We also noted that high AK144841 expression correlated with a
low expression of the aforementioned genes and with the tumorigenic potential of
cell lines. These findings suggest that AK144841 could contribute to the
dedifferentiation program of tumor-forming keratinocytes and to molecular
cascades leading to tumor development.