MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus

Cell Death & Disease
Jack D GodfreyMartin D Bushell

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in both gain-of-function TP53 mutations and metastasis, but this has not been fully explored in PDAC. Here we set out to identify miRNAs which are specifically dysregulated in metastatic PDAC. To achieve this, we utilised established mouse models of PDAC to profile miRNA expression in primary tumours expressing the metastasis-inducing mutant p53R172H and compared these to two control models carrying mutations, which promote tumour progression but do not induce metastasis. We show that a subset of miRNAs are dysregulated in mouse PDAC tumour tissues expressing mutant p53R172H, primary cell lines derived from mice with the same mutations and in TP53 null cells with ectopic expression of the orthologous human mutation, p53R175H. Specifically, miR-142-3p is downregulated in all of these experimental models. We found that DNA methyltransferase 1 (Dnmt1) is upregulated in tumour tissue and cell lines, which express p53R172...Continue Reading

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Citations

May 23, 2019·Molecular and Cellular Biochemistry·Zenghui LiJing Wang
Feb 23, 2020·International Journal of Molecular Sciences·Katarzyna A RoszkowskaMaciej B Olszewski
Jan 9, 2021·Cell Death & Disease·Sergey ParfenyevNiсkolai A Barlev
Nov 26, 2020·International Journal of Molecular Sciences·Young-Ho Ahn, Yoon Ho Ko
Aug 28, 2021·Cancers·Yen-Ting ChiangYung-Luen Yu
Sep 30, 2021·Journal of Hematology & Oncology·Jiahao HuMingyu Chen
Dec 17, 2019·Molecular Therapy. Nucleic Acids·Xiaomin LiuZhongliang Ma
Sep 15, 2020·Seminars in Cancer Biology·Song ChenLianxin Liu

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Datasets Mentioned

BETA
GSE50827
GSE71729

Methods Mentioned

BETA
targeted mutation
feature extraction
transfections
transfection

Software Mentioned

Agilent
Methyl primer Express
BioEdit
BiQ Analyzer
ImageJ
Genespring

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