miRNAs in human cancer

Farazi, Thalia A.; Spitzer, Jessica; Morozov, Pavel; Tuschl, Thomas

doi:10.1002/path.2806

Cited by 848 publications

(661 citation statements)

References 185 publications

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“…MiRNAs contribute to the pathogenesis of CRC by regulating the expression of oncogenes and tumor suppressors and also by directly functioning as oncogenes or tumor suppressors (15,16). The role of miRNAs in the development of metastasis has been demonstrated in several cancer types, including breast cancer, hepatocellular carcinomas, head and neck cancer and brain tumors (17).…”

Section: Introductionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

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Abstract. MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and Western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

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“…After binding to the RISC microRNAs regulate gene expression posttranscriptionally by a binding of specific mRNA, depending on the target mRNA they can function as oncogene or tumor suppressor. [10][11][12][13][14][15][16][17][18][19] Several microRNAs or miR-families involved in stem cell signaling are identified, for example, miR-21 involved in self-renewal and apoptosis, the let-7 family and miR-200 family involved in pluripotency and cell differentiation. 34 The miR-200 family is down-regulated in cells undergoing epithelial-to-mesenchymal transition (EMT).…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs regulate many genes known to play important roles in oncogenesis, angiogenesis and tissue differentiation. [10][11][12][13][14][15] In all, 1527 human microRNA sequences have been discovered to date and the number is increasing (miRBase. http:// www.mirbase.org, last accesses February 2012).…”

mentioning

confidence: 99%

“…MicroRNAs have highly tissue-specific expression patterns. [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.…”

mentioning

confidence: 99%

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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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“…They can regulate functional gene expression, and abundant evidence has revealed their aberrant expression in various types of human cancers. [5][6][7] In addition, reliable methods for extracting miRNAs from bodily fluids, such as serum, have been well developed and well validated. 8,9 Therefore, serum miRNAs could represent novel biomarkers for PCa.…”

Section: Introductionmentioning

confidence: 99%

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

Zhang¹,

Xiao²,

Cao³

et al. 2013

Asian J Androl

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The skeleton is the most common metastatic organ in patients with prostate cancer (PCa). Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia (BPH), 20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa). A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P,0.001). There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall's bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P50.012 and P,0.001, respectively). The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis, using Pearson's bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

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miRNAs in human cancer

Cited by 848 publications

References 185 publications

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

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