MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior

Department of Surgical and Gastroenterological Sciences, University of Verona, Verona, Veneto, Italy
Journal of Clinical Oncology (Impact Factor: 18.43). 11/2006; 24(29):4677-84. DOI: 10.1200/JCO.2005.05.5194
Source: PubMed


We investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies.
Using a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas.
Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis.
These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.

10 Reads
  • Source
    • "To date, every type of cancers analysed by miRNA profiling has shown significantly different miRNA profiles compared with normal cells from the same tissues. Several other genome-wide profiling studies have been performed on various cancer types, including chronic lymphocytic leukemia [7], breast cancer [8], glioblastoma [9], hepatocellular carcinoma [10], lung cancer [11], colon cancer and endocrine pancreatic tumours [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (MiRNAs) are small non-coding RNAs (18-25nt) that regulate gene expression mainly through affecting post-transcriptional modification. Osteosarcoma is an aggressive sarcoma of the bone characterized by a high level of genetic instability and recurrent DNA deletions and amplifications. microRNAs (miRNAs) play an important role in cancer cell growth and migration, however, the potential roles of miRNAs in osteosarcoma remain largely uncharacterized. In this paper, miR-199a and miR-34a were discussed the mechanisms of apoptosis using micrRNA mimics in human osteosarcoma cells. The results demonstrated that miR-199a and miR-34a could induce the apoptosis of human osteosarcoma cells via p53 signaling pathway.
    Bioscience Reports 06/2014; 34(4). DOI:10.1042/BSR20140084 · 2.64 Impact Factor
  • Source
    • "However, the only up-regulated validated microRNA identified in our signature that could discriminate between colonic hepatic metastasis and primary hepatocellular carcinoma was hsa-miR-103. The relevance of this miRNA in cancer has been assessed in pancreatic, bladder, esophageal, gastric and breast tumors [29], [90]–[93]. High levels of hsa-miR-103 were correlated to poor survival in esophageal cancer and are associated to metastatic disease in breast and gastric cancer. Particularly, hsa-miR-103 upregulation was detected in gastric cancer patients bearing positive lymph nodes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor.
    PLoS ONE 06/2014; 9(6):e96670. DOI:10.1371/journal.pone.0096670 · 3.23 Impact Factor
  • Source
    • "Today, it has been proved that deregulation in expression of miRNAs has important role in the pathogenesis of genetic and multifactorial cancers, as well as pancreatic cancer [5, 6]. Because the majority of human protein-coding genes could be regulated by miRNAs, equally it was assumed that miRNAs could have several target genes [7] though miRNAs are apt to downregulate target mRNAs [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods: 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA-mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results: This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion: Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.
    BioMed Research International 05/2014; 2014(9):534821. DOI:10.1155/2014/534821 · 3.17 Impact Factor
Show more