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 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:We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93,miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most upregulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells.
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:A critical question in molecular oncology is how extensive is the involvement of non-codingRNAs (ncRNAs) in human tumorigenesis. Herein, we report that a large fraction of genomic ultraconserved regions (UCRs) are encoding a particular set of ncRNAs and are altered in human cancers. We show that UCRs are frequently located at fragile sites and genomic regions involved in cancers, and that genome-wide UCRs profiling reveals distinct signatures in human leukemias and carcinomas. We proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells, and we identified UCRs whose expression may be regulated by miRNAs abnormally expressed in human chronic lymphocytic leukemia (CLL). Our findings argue that non-coding genes are involved in tumorigenesis at a greater extent as thought before and offer the perspective of identification of signatures associated with diagnosis, prognosis and response to treatment composed by various categories of ncRNA genes.
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:Background. Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results. We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusions. This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.