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- Title
Exploring the Wnt Pathway-Associated LncRNAs and Genes Involved in Pancreatic Carcinogenesis Driven by Tp53 Mutation.
- Authors
Wang, Qi; Jiang, He; Ping, Chen; Shen, Ruizhe; Liu, Tingting; Li, Juanjuan; Qian, Yuting; Tang, Yanping; Cheng, Shidan; Yao, Weiyan; Wang, Lifu
- Abstract
Purpose: 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 mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras ; LSL- Tp53 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.
- Subjects
PANCREATIC cancer treatment; WNT proteins; NON-coding RNA; CARCINOGENESIS; P53 protein; GENETIC mutation; DUCTAL carcinoma
- Publication
Pharmaceutical Research, 2015, Vol 32, Issue 3, p793
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-013-1269-z