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Exploring the Wnt Pathway-Associated LncRNAs and Genes Involved in Pancreatic Carcinogenesis Driven by Tp53 Mutation

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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 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.

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Abbreviations

ChIP:

Chromatin immunoprecipitation

DT-PCa:

PDAC cell line

lncRNAs:

long non-coding RNAs

PanIN:

pancreatic intraepithelial neoplasia

PDAC:

pancreatic ductal adenocarcinoma

SH-PAN:

PanIN cell line

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ACKNOWLEDGMENTS AND DISCLOSURES

We thank Professor David A Tuveson and Dr. Sunil R. Hingorani for genetically engineering mouse models of PanIN and PDAC, cell lines SH-PAN and DT-PCa, and helpful advices. Supported in part by National Natural Science Foundation of China (81272263, 30971130, 30672385), and Grant of Science and Technology Commission of Shanghai Municipality (11JC1407601).

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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Authors and Affiliations

  1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Qi Wang, He Jiang, Chen Ping, Ruizhe Shen, Tingting Liu, Juanjuan Li, Yuting Qian, Yanping Tang, Shidan Cheng, Weiyan Yao & Lifu Wang

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  1. Qi Wang
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  2. He Jiang
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Corresponding authors

Correspondence to Weiyan Yao or Lifu Wang.

Additional information

Q. Wang, H. Jiang and C. Ping contributed equally to this work.

Electronic supplementary material

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Supplementary Figure S1

Validation of the differentially expressed mRNAs in Wnt pathway. Real-time PCR was employed. Results represented the mean values and the standard deviations of three independent experiments. The validation results of the 12 mRNAs showed that the microarray data correlated well with the real-time PCR results. (JPEG 36 kb)

High resolution image (TIFF 55 kb)

Supplementary Table S1

The differentially expressed lncRNAs in DT-PCa cells compared to SH-SAN cells (DOC 896 kb)

Supplementary Table S2

The differentially expressed mRNAs in DT-PCa cells compared to SH-SAN cells (DOC 2082 kb)

Supplementary Table S3

Pathway analysis according to th differentially expressed genes (DOC 34 kb)

Supplementary Table S4

The detail description of the selected lncRNAs (DOC 32 kb)

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Wang, Q., Jiang, H., Ping, C. et al. Exploring the Wnt Pathway-Associated LncRNAs and Genes Involved in Pancreatic Carcinogenesis Driven by Tp53 Mutation. Pharm Res 32, 793–805 (2015). https://doi.org/10.1007/s11095-013-1269-z

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  • DOI: https://doi.org/10.1007/s11095-013-1269-z

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