Project description:MicroRNAs are a class of small non-coding RNAs that control gene expression by targeting messenger RNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, microRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where microRNA signatures were associated with specific clinico-biological features. Here, we show that, in comparison to normal breast tissue, microRNAs are also aberrantly expressed in human breast cancer. The overall microRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated microRNAs being mir-125b, mir-145, mir-21, mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify microRNAs whose expression was correlated with specific breast cancer bio-pathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion or proliferation index.
Project description:Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous miRNAs are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of 5 miRNAs including the 3 most upregulated ones (miRs 221, 222, 146) distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was upregulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the upregulation (11-19 fold) of miRs 221, 222 and 146 was strongest showed dramatic loss of KIT transcript and Kit protein. In five of 10 such cases this was associated with germline single nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that upregulation of several miRs and down regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their downregulation.
Project description:We studied the value of the microRNAs as a signature for Chronic lymphocytic leukemia (CLL) patients with specific chromosomal abnormalities. We found that MiR-181b is abiomarker of disease progression in Chronic Lymphocytic Leukemia
Project description:MicroRNA-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia patients >=60 years.
Project description:Acute myeloid leukemia (AML) carrying NPM1 mutations and cytoplasmic nucleophosmin (NPMc+ AML) accounts for about one-third of adult AML and shows distinct features, including a unique gene expression profile. MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nucleotides in length that have been linked to the development of cancer. Here, we investigated the role of miRNAs in the biology of NPMc+ AML. The miRNA expression was evaluated in 85 adult de novo AML patients characterized for subcellular localization/mutation status of NPM1 and FLT3 mutations using a custom microarray platform. Data were analyzed by using univariate t test within BRB tools. We identified a strong miRNA signature that distinguishes NPMc+ mutated (n = 55) from the cytoplasmic-negative (NPM1 unmutated) cases (n = 30) and includes the up-regulation of miR-10a, miR-10b, several let-7 and miR-29 family members. Many of the down-regulated miRNAs including miR-204 and miR-128a are predicted to target several HOX genes. Indeed, we confirmed that miR-204 targets HOXA10 and MEIS1, suggesting that the HOX up-regulation observed in NPMc+ AML may be due in part by loss of HOX regulators-miRNAs. FLT3-ITD+ samples were characterized by up-regulation of miR-155. Further experiments demonstrated that the up-regulation of miR-155 was independent from FLT3 signaling. Our results identify a unique miRNA signature associated with NPMc+ AML and provide evidence that support a role for miRNAs in the regulation of HOX genes in this leukemia subtype. Moreover, we found that miR-155 was strongly but independently associated with FLT3-ITD mutations.
Project description:MicroRNAs are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules can represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme (GBM), the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly upregulated in glioblastoma and a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, miR-181c, which are down-regulated in glioblastoma.