Profiling of 95 MicroRNAs in Pancreatic Cancer Cell Lines and Surgical Specimens by Real‐Time PCR Analysis

Zhang, Yuqing; Li, Min; Wang, Hao; Fisher, William E.; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

doi:10.1007/s00268-008-9833-0

Cited by 280 publications

(236 citation statements)

References 38 publications

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“…Interestingly, the role of miR-95 with respect to cellular proliferation and cancer seems to be highly tissue dependent. While it was suggested to have proproliferative function in prostate, lung and pancreatic cancers 22,24,34 , its downregulation in head and neck cancers as well as in glioblastomas suggests a tumour-suppressive role for miR-95 in these tissues 35,36 .…”

Section: Discussionmentioning

confidence: 99%

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

et al. 2014

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Sulfatases are key enzymatic regulators of sulfate homeostasis with several biological functions including degradation of glycosaminoglycans (GAGs) and other macromolecules in lysosomes. In a severe lysosomal storage disorder, multiple sulfatase deficiency (MSD), global sulfatase activity is deficient due to mutations in the sulfatase-modifying factor 1 (SUMF1) gene, encoding the essential activator of all sulfatases. We identify a novel regulatory layer of sulfate metabolism mediated by a microRNA. miR-95 depletes SUMF1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. This blocks autophagy-mediated degradation, causing cytoplasmic accumulation of autophagosomes and autophagic substrates. By targeting miR-95 in cells from MSD patients, we can effectively increase residual SUMF1 expression, allowing for reactivation of sulfatase activity and increased clearance of sulfated GAGs. The identification of this regulatory mechanism opens the opportunity for a unique therapeutic approach in MSD patients where the need for exogenous enzyme replacement is circumvented.

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Section: Discussionmentioning

confidence: 99%

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

et al. 2014

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“…[15][16][17][18][19] In pancreatic adenocarcinomas, the expression of miR-15b, miR-21, miR-95, miR-103, miR-107, miR-148a, miR-155, miR-196a, miR-200, miR-210, miR-217, miR-221, miR-222 and miR-375 are different from tissue of normal pancreas and chronic pancreatitis. 17,[20][21][22][23][24][25][26][27] The results reported by Bloomston et al 20 and Szafranska et al 26 give promises of significant clinical impact of microRNA expression profiles to separate tissue from pancreatic adenocarcinomas from normal pancreas and chronic pancreatitis. The study by Szafranska et al 26 included a combination of two microRNAs (the difference between miR-196a and miR-217) to separate pancreatic adenocarcinomas and chronic pancreatitis (ASURAGEN-test).…”

mentioning

confidence: 97%

“…20,21,23,24 MicroRNAs are stable in formalin-fixed paraffin-embedded samples. 28,29 Tumor cells in pancreatic ductal adenocarcinomas are often located in small groups surrounded by an abundant stromal tissue 30 and information related to microRNAs from the stromal tissue may be lost if micro-dissection is applied.…”

mentioning

confidence: 99%

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Schultz

Werner

Willenbrock³

et al. 2012

Modern Pathology

137

106

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MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b* and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P ¼ 2.06 Â 10 À 54 ) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from nonneoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer. Modern Pathology (2012Pathology ( ) 25, 1609Pathology ( -1622 doi:10.1038/modpathol.2012; published online 10 August 2012Keywords: ampullary adenocarcinoma; chronic pancreatitis; microRNA; normal pancreas; pancreatic adenocarcinoma; pancreatic cancer Pancreatic cancer is the fourth most common cause of cancer death in United States and Europe. 1,2 Less than 20% of the patients can be operated with curative intent and the 5-year survival after surgery is below 20%. 3 Early diagnosis is difficult and the clinical and histological similarities between pancreatic cancer and chronic pancreatitis further complicate the differentiation between inflammation and cancer.

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“…miR-222 has been shown to be up-regulated in gastric cancer, thyroid tumors, pancreatic cancer, childhood B-cell precursor acute lymphoblastic leukemia and hepatic cell cancers (23,(31)(32)(33)(34). The overexpression of miR-222 is found to be correlated with the resistance to hormone treatment and aggressiveness in prostate carcinoma (35,36).…”

Section: Discussionmentioning

confidence: 96%

5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro

Bai¹

2009

Oncol Rep

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Abstract. MicroRNAs (miRNAs) have recently taken center stage in the field of human molecular oncology. Most of the chemotherapeutics are able to interfere with nucleic acid metabolism and gene expression. The purpose of this study was to determine how 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) modify the expression profiles of miRNAs in HCT-8 and HCT-116 colon cancer cells and whether the pharmacodynamic mechanisms of the chemotherapeutics could rely in part on their influence on miRNA expression. The expression profiles of miRNAs were determined using a miRNA microarray containing 856 human miRNA probes. The expression of selected miRNAs was then validated by real-time RT-PCR. Fifty-six up-and 50 down-regulations of miRNA expression with statistical significance were identified in colon cancer cells following exposure to 5-FU or L-OHP compared to matched control cells. The down-regulations of miR-197, miR-191, miR-92a, miR-93, miR-222 and miR-1826, whose expression was significantly down-regulated in both cell lines after the treatment of one drug or in one cell line following exposure to either drug, were further validated. Analysis of the relevant literature indicated that, in line with the tumor suppressive activity of 5-FU and L-OHP, the six down-regulated miRNAs might function as oncogenes due to their overexpression in cancers, and some of them correlated with the poor prognosis and treatment-resistance of cancer. In conclusion, we identify the modification of miRNA expression profiles in colon cancer cells following exposure to 5-FU and L-OHP, and our results indicate that their pharmacodynamic mechanisms could rely in part on their influence on the down-regulated miRNA expression.Further studies are needed to determine whether these miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference.

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Profiling of 95 MicroRNAs in Pancreatic Cancer Cell Lines and Surgical Specimens by Real‐Time PCR Analysis

Cited by 280 publications

References 38 publications

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro

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