MicroRNA-148a is down-regulated in human pancreatic ductal adenocarcinomas and regulates cell survival by targeting CDC25B

Liffers, Sven-T; Münding, Johanna; Vogt, Markus; Kuhlmann, Jan Dominik; Verdoodt, Berlinda; Nambiar, Sandeep; Maghnouj, Abdelouahid; Mirmohammadsadegh, Alireza; Hahn, Stephan A.; Tannapfel, Andrea

doi:10.1038/labinvest.2011.99

Cited by 104 publications

(94 citation statements)

References 34 publications

(41 reference statements)

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“…Cdc25B was identified as a novel miRNA-148a target. Cdc25B was down-regulated at the protein level in miR148a overexpressing IMIM-PC2-cells, and in transiently transfected pancreatic cell lines, as well as in human pancreatic ductal adenocarcinoma (Liffers et al, 2011). Cdc5B plays a minor role in the pathogenesis and/or progression of vulvar carcinoma, which was associated with malignant features and aggressive cancer phenotypes, but not independently correlated to prognosis (Wang et al, 2010).…”

Section: Discussionmentioning

confidence: 98%

“…Cdc25B was identified as a novel miRNA-148a target which may confer a proliferative advantage in human pancreatic ductal adenocarcinoma (Liffers et al, 2011). Overexpression of Cdc25B, Cdc25C and phosphoCdc25C (Ser216) in vulvar squamous cell carcinoma is associated with malignant features and aggressive cancer phenotypes (Wang et al, 2010).…”

Section: Knockdown Of Cdc25b In Renal Cell Carcinoma Is Associated Wimentioning

confidence: 99%

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Knockdown of Cdc25B in Renal Cell Carcinoma is Associated with Decreased Malignant Features

Yu¹,

Zhang²,

Zhang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.

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Section: Discussionmentioning

confidence: 98%

Section: Knockdown Of Cdc25b In Renal Cell Carcinoma Is Associated Wimentioning

confidence: 99%

Knockdown of Cdc25B in Renal Cell Carcinoma is Associated with Decreased Malignant Features

Yu¹,

Zhang²,

Zhang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Reduces proliferation and invasion capacity in vitro and in vivo [37] miR-148a Tumor suppressor miRNA mimic Drastic inhibition of the invasive properties of HCC [109] miR-148a Tumor suppressor miRNA mimic and miRNA-expressing vector Suppresses the EMT and metastasis of HCC [110] miR-148a Tumor suppressor Lentiviral system Inhibits tumor cell growth and colony formation [111] …”

Section: Manipulation Of Mirna Expression Levels As a Therapeutic Strmentioning

confidence: 99%

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

2016

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Pancreatic cancer is a devastating malignancy that ranks as the fourth leading cause of cancerrelated deaths worldwide. Dismal prognosis is mainly attributable to limited knowledge of the molecular pathogenesis of the disease. miRNAs have been found to be deregulated in pancreatic cancer, affecting several steps of initiation and aggressiveness of the disease by regulating important signaling pathways, such as the KRAS and Notch pathways. Moreover, the effect of miRNAs on regulating cell cycle events and expression of transcription factors has gained a lot of attention. Recent studies have highlighted the application of miRNAs as biomarkers and therapeutic tools. The current review focuses on latest advances with respect to the roles of miRNAs in pancreatic ductal adenocarcinoma associated signaling pathways and miRNA-based therapeutics. KEYWORDS• antisense oligonucleotides • miRNAs • pancreatic cancer Pancreatic cancer overview Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic neoplasms and accounts for greater than 85% of the clinical cases [1]. The disease develops via acinar-ductal metaplasia and neoplastic precursor lesions [2]. In the USA alone, 48,960 new cases of pancreatic cancer were expected to occur in 2015, with an estimated 40,560 deaths, about the same number in women (19,850) as in men (20,710). Over 96% are cancers arising from exocrine pancreas. Endocrine carcinomas are often diagnosed at a younger age and exhibit a better prognosis. From 2007 to 2011, mortality rates increased slightly by 0.3% per year. For all stages combined, the 1-and 5-year relative survival rates are 28 and 7%, respectively. For the small percentage of people diagnosed with local disease (9%), the 5-year survival is 26%, while more than half of patients (53%) are diagnosed at a late stage for which 1-and 5-year survival rates reach 15 and 2%, respectively [3]. These numbers are a staggering example of the poor prognosis associated with PDAC.While new therapeutic options are emerging for nonhematologic malignancies, molecular-targeted therapies for pancreatic cancer have failed to make any positive impact on patient survival. In 1993, the Nobel Prize-winning discovery of small interference RNAs (siRNAs) led to an outburst of knowledge on RNA interference and gene regulation [4]. Since then, thousands of research studies have described the functional role of small noncoding RNAs, named miRNAs, in a vast panel of human pathologies. In 2002, a small genomic region in chromosome 13q14 comprising miR-15a and miR-16-1 genes was found to be commonly deleted in chronic lymphocytic leukemia, For reprint orders, please contact: reprints@futuremedicine.com

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“…Recently, deregulation of miRNAs expression has been correlated to diagnosis, prognosis and chemotherapy resistance of pancreatic cancer (Chakraborty et al, 2011;Dhayat et al, 2011). Among the several miRNAs reported to be up regulated in pancreatic cancer such as miR-21, miR-221/222, miR-25, miR-27a, miR-210, miR-200b, miR-148a,b, miR-196a-2, miR-155, and members of the miR-17-92 family (Chakraborty et al, 2011;Liffers et al, 2011;Nana-Sinkam & Croce, 2011;Zhang et al, 2011), the oncomiR miR-21 appears of high relevance as potential therapeutic target in pancreatic cancer, regulating proliferation, invasion, apoptosis and chemosensitivity (Ali et al, 2010;Giovannetti et al, 2010;Hwang et al, 2010;Park et al, 2009). miR-21 mimics, transfected into MIA PaCa-2 pancreatic cancer cells, have been shown to upregulate Bcl-2, to downregulate Bax expression, to decrease chemosensitivity to gemcitabine and to increase proliferation as compared with control cells.…”

Section: Micrornasmentioning

confidence: 99%