scholarly journals Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148aon gene regulation

2018 ◽  
Vol 109 (6) ◽  
pp. 2013-2026 ◽  
Author(s):  
Tetsuya Idichi ◽  
Naohiko Seki ◽  
Hiroshi Kurahara ◽  
Haruhi Fukuhisa ◽  
Hiroko Toda ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Passenger Strand

scholarly journals Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2731
Author(s):  
Takako Tanaka ◽  
Reona Okada ◽  
Yuto Hozaka ◽  
Masumi Wada ◽  
Shogo Moriya ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Topoisomerase Ii ◽  
Survival Rates ◽  
Ectopic Expression ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Mirna Signature ◽  
Topoisomerase Ii Alpha ◽  
Passenger Strand ◽  
One Year

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA (miRNA) signature analysis of PDAC revealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.

scholarly journals Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis

2020 ◽  
Vol 21 (18) ◽  
pp. 6459
Author(s):  
Hiroki Shimomura ◽  
Reona Okada ◽  
Takako Tanaka ◽  
Yuto Hozaka ◽  
Masumi Wada ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ectopic Expression ◽  
In Silico Analysis ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Binding Partner ◽  
Passenger Strand ◽  
Silico Analysis ◽  
Mirna Expression Signature

Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma

Pathology ◽  
2003 ◽  
Vol 35 (1) ◽  
pp. 14-24 ◽  
Author(s):  
Andrew V. Biankin ◽  
James G. Kench ◽  
Floriaan P. Dijkman ◽  
Sandra A. Biankin ◽  
Susan M. Henshall
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Precursor Lesions

Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma

Pathology ◽  
2003 ◽  
Vol 35 (1) ◽  
pp. 14-24 ◽  
Author(s):  
Andrew V. Biankin ◽  
James G. Kench ◽  
Floriaan P. Dijkman ◽  
Sandra A. Biankin ◽  
Susan M. Henshall
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Precursor Lesions

Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8

2019 ◽  
Vol 64 (6) ◽  
pp. 521-534 ◽  
Author(s):  
Haruhi Fukuhisa ◽  
Naohiko Seki ◽  
Tetsuya Idichi ◽  
Hiroshi Kurahara ◽  
Yasutaka Yamada ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Significance ◽  
Ductal Adenocarcinoma

Abstract B52: MicroRNAs and SEL1L gene regulation in human pancreatic ductal adenocarcinoma

2010 ◽  
Author(s):  
Qian Liu ◽  
Jinyun Chen ◽  
Chris Amos ◽  
Ann Killary ◽  
Subrata Sen ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma

Molecular pathogenesis of pancreatic ductal adenocarcinoma and clinical implications

2001 ◽  
Vol 10 (1-2) ◽  
pp. 1-23 ◽  
Author(s):  
Conor J Magee ◽  
William Greenhalf ◽  
Nathan Howes ◽  
Paula Ghaneh ◽  
John P Neoptolemos
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Pathogenesis ◽  
Ductal Adenocarcinoma ◽  
Clinical Implications

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma

2000 ◽  
Vol 15 (11) ◽  
pp. 1333-1338 ◽  
Author(s):  
Koji Uno ◽  
Takeshi Azuma ◽  
Masatsugu Nakajima ◽  
Kenjiro Yasuda ◽  
Takanobu Hayakumo ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Significance ◽  
Pancreatic Juice ◽  
Ductal Adenocarcinoma ◽  
Cathepsin E
Sign in / Sign up

Export Citation Format

Share Document