Expression profiling identifies microRNA signature in pancreatic cancer

Abstract

microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real‐time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pancreatitis and nine pancreatic cancer cell lines. Hierarchical clustering was able to distinguish tumor from normal pancreas, pancreatitis and cell lines. The PAM algorithm correctly classified 28 of 28 tumors, 6 of 6 normal pancreas and 11 of 15 adjacent benign tissues. One hundred microRNA precursors were aberrantly expressed in pancreatic cancer or desmoplasia (p < 0.01), including microRNAs previously reported as differentially expressed in other human cancers (miR‐155, miR‐21, miR‐221 and miR‐222) as well as those not previously reported in cancer (miR‐376a and miR‐301). Most of the top aberrantly expressed miRNAs displayed increased expression in the tumor. Expression of the active, mature microRNA was validated using a real‐time PCR assay to quantify the mature microRNA and Northern blotting. Reverse transcription in situ PCR showed that three of the top differentially expressed miRNAs (miR‐221, ‐376a and ‐301) were localized to tumor cells and not to stroma or normal acini or ducts. Aberrant microRNA expression may offer new clues to pancreatic tumorigenesis and may provide diagnostic biomarkers for pancreatic adenocarcinoma. © 2006 Wiley‐Liss, Inc.

Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

“…Under pathologic conditions, miR-155 has been associated with a number of human neoplastic disorders. Studies have shown that miR-155 accumulates in chronic lymphocytic leukemia (34), lymphomas (30,35), breast cancer, and pancreatic cancer (36,37). Our findings extend the information on miR-155 expression in human cells by demonstrating its presence in synovial fibroblasts.…”

MicroRNA-155 Expression has Prognostic Value in Patients with Non-small Cell Lung Cancer and Digestive System Carcinomas

“…Recent studies have showed that miR-155 gene is one of the miRNAs most consistently over-expressed in both hematopoietic malignancies and solid tumors, such as leukemia (O'Connell et al, 2008;Raponi et al, 2009), thyroid carcinoma (Nikiforova et al, 2008), breast cancer (Iorio et al, 2005;Greither et al, 2010), cervical cancer (Wang et al, 2008), colorectal cancer , pancreatic ductal adenocarcinoma (PDAC) (Lee et al, 2007;Szafranska et al, 2007), hepatocellular carcinoma (Han et al, 2012;Huang et al, 2012), and lung cancer (Yanaihara et al, 2006;Donnem et al, 2011). Therefore, overexpression miR-155 may be a general characteristic of cancer and be detected as a biomarker for cancer diagnosis and prognosis.…”

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

“…[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).…”