Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28157704
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Overlooked FANCD2 variant encodes a promising, portent tumor suppressor, and
alternative polyadenylation contributes to its expression
#MMPMID28157704
Han B
; Shen Y
; Zhang P
; Jayabal P
; Che R
; Zhang J
; Yu H
; Fei P
Oncotarget
2017[Apr]; 8
(14
): 22490-22500
PMID28157704
show ga
Fanconi Anemia (FA) complementation group D2 protein (FANCD2) is the center of
the FA tumor suppressor pathway, which has become an important field of
investigation in human aging and cancer. Here we report an overlooked central
player in the FA pathway, FANCD2 variant 2 (FANCD2-V2), which appears to perform
more potent tumor suppressor-function compared to the known variant of FANCD2,
namely, FANCD2-V1. Detailed analysis of the FANCD2 gene structure indicated a
proximal and distal polyadenylation site (PAS), associated with V2 and V1
transcripts accordingly. RNA polymerase II Chromatin immunoprecipitation (ChIP)
targeting the two PAS-regions determined lesser binding of RNA pol II to DNA
fragments in the distal PAS region in non-malignant cells compared to malignant
cells. Conversely, the opposite occurred in the proximal PAS region. Moreover,
RNA immunoprecipitation (RIP) identified that U2 snRNP, a major component of RNA
splicing complex that interacts with the 3'end of an intron, showed greater
binding to the last intron of the FANCD2-V1 transcript in malignant cells
compared to the non-malignant cells. Importantly, our data showed that in human
tissue samples, the ratio of V2 /V1 expression in lung, bladder, or ovarian
cancer correlates inversely with the tumor stages/grades. Therefore, these
findings provide a previously unrecognized central player FANCD2-V2 and thus
novel insights into human tumorigenesis, and indicate that V2/V1 can act as an
effective biomarker in assisting the recognition of tumor malignance.
|Alternative Splicing
[MESH]
|Biomarkers, Tumor/*genetics
[MESH]
|Carcinogenesis/genetics
[MESH]
|Fanconi Anemia Complementation Group D2 Protein/*genetics
[MESH]
free
free
free
