We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most ...[more]
Project description:MicroRNA expression profiles can distinguish normal B cells from malignant B cells in chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. We evaluated the microRNA expression profiles of 94 samples of CLL cells for which ZAP-70 expression, mutations in the rearranged IgVH gene, and the time from diagnosis to initial treatment were known. We also investigated the presence of abnormalities in the genomic sequence of 42 microRNA genes.
Project description:Profiling array: in order to investigate the microRNAs differentially expressed between osteosarcoma and their normal bone counterpart. Specimens were kept at 4 C in RNAlater for up to 1 week, then stored at 80 C. When formal pathologic interpretation of histology from other portions of the biopsy specimen rendered a diagnosis of osteosarcoma, the RNA-preserving tissue specimens were banked and annotated. In preparation for these specific experiments, total RNA was extracted from banked specimens with the TRIzol reagent and method (Invitrogen). Control samples were derived from to-be-discarded bone fragments obtained from similarly consented patients undergoing debridement surgeries for acute, traumatic injuries to the long bones.
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:MicroRNA (miRNA) expression profiles for colon cancers were examined to investigate the miRNA involvement in colon carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate colon cancers from noncancerous colon tissues.
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:MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate the miRNA involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues.
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:MicroRNA expression profiles in response to LBH589 were examined in order to identify HDACi-induced alterations in miRNA expression that regulate apoptotic signaling in chronic lymphocytic leukemia.plasia. miRNA microarray analysis identified unique alterations in miRNA profile that could be used to identify new pathways for apoptosis regulation in CLL.