Exploring the Wnt pathway-associated LncRNAs and genes involved in pancreatic carcinogenesis driven by Tp53 mutation.
OBJECTIVE
Study the contribution of long non-coding RNAs (lncRNAs) to progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC).


METHODS
We explored lncRNAs profilings in PanIN cell line (SH-PAN) isolated from Pdx-1-Cre; LSL-Kras (G12D/+) mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras (G12D/+) ; LSL- Tp53 (R172H/+) mice by lncRNAs microarray, and detected expression of lncRNAs and genes in PDAC by Real-time PCR, Western blot, ChIP and immunohistochemistry.


RESULTS
Eight lncRNAs and five protein-coding genes, associated with Wnt pathway, were identified with more than five-fold changes between DT-PCa cells and SH-PAN cells. Of them, lincRNA1611 and Ppp3ca were validated significantly high expression in DT-PCa cells and in 22 of 26 fresh resected human PDAC tissues, compared to SH-PAN cells and normal pancreatic tissues, respectively. Moreover, Tp53 mutation status displayed a positive correlation with lincRNA1611 or Ppp3ca level. Immunohistochemical staining for Ppp3ca was weak or lack in 91 of 107 normal pancreatic tissues, 24 of 29 PanIN-I and 13 of 16 PanIN-II tissues, however, was strong in 10 of 27 PanIN-III and 62 of 107 PDAC tissues post operation.


CONCLUSIONS
LincRNA1611 and Ppp3ca were high expression in PDAC and may serve as new potential targets for intervention of the disease.
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
Qi
Q
Wang
He
H
Jiang
Chen
C
Ping
Ruizhe
R
Shen
Tingting
T
Liu
Juanjuan
J
Li
Yuting
Y
Qian
Yanping
Y
Tang
Shidan
S
Cheng
Weiyan
W
Yao
Lifu
L
Wang
D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008817:Mice, Mutant Strains; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*
D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019703:Calcineurin; C525673:PPP3CA protein, human