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Over-expression of miR-18b is associated with the grade of malignancy of hepatocallular carcinoma

ABSTRACT: Aberrant expression of microRNA (miRNA) is closely associated with carcinogenesis. The malignancy of the hepatocellular carcinoma (HCC) is prescribed in the degree of histological differentiation. Poorly differentiated HCC is generally more malignant prognosis than well differentiated HCC. We analyzed the miRNA expression profiles in 110 HCC (60 moderately differentiated, 30 poorly differentiated, and 20 well differentiated HCC) by using microarray in order to establish the novel biomarker for the degree of histological differentiation and forecasting relapse of HCC. The expression level of 12 miRNAs was significantly different according to the degree of histological differentiation. The expression level of miR-18b in poorly differentiated HCC was significantly higher than that in well differentiated HCC. Based on the target search algorithm and argonaute 2 (Ago2) immunoprecipitation study for target binding assay, miR-18b can control the expression of trinucleotide repeat containing 6B (TNRC6B) as a target. Over expression of miR-18b and down regulation of TNRC6B accelerated the activity of cell proliferation and lost ability of cell adhesion in two hepatoma cell lines. Low expression of miR-18b is significantly decreased the relapse free rate after surgical resection. In conclusion, expression pattern of miR-18b is a marker of an important determinant in the control of cell proliferation and adhesion and also prediction of clinical course. From a clinical point of view, our study emphasizes miR-18b as a diagnostic and prognostic marker for HCC progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31164 | GEO | 2013/04/10

SECONDARY ACCESSION(S): PRJNA144801

REPOSITORIES: GEO

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Project description:Brain tumor neurospheres (BTCSs) are cancer cells with neural stem cell-like properties found in the fatal brain tumor glioblastoma multiforme (GBM). These cells account for less than 1% of total tumor cells, are poorly differentiated and are believed to be involved in tumor induction, progression, treatment resistance and relapse. Specific miRNAs play important roles in modulating the proliferation and differentiation of neural stem cells, therefore, we aimed to identify miRNAs controlling differentiation in GBM-BTSCs through high throughput screening miRNA array profiling. We compared the miRNA expression profiles at the neurosphere state and upon 4 and 14days of differentiation by using LIMMA, finding 21 differentially expressed miRNAs : hsa-miR-103, hsa-miR-106a, hsa-miR-106b, hsa-miR-15b, hsa-miR-17, hsa-miR-19a, hsa-miR-20a, hsa-miR-25, hsa-miR-301a and hsa-miR-93 were found up-regulated upon differentiation, while hsa-miR-100, hsa-miR-1259, hsa-miR-21, hsa-miR-22, hsa-miR-221, hsa-miR-222, hsa-miR-23b, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a and hsa-miR-29b were down-regulated. Expression of 11 of the 21 miRNAs was examined by qPCR and 7 of them were validated: hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222 increased their expression upon differentiation, while hsa-miR-93 and hsa-miR-106a were inhibited. Functional studies demonstrated that miR-21 over-expression induced the expression of glial and/or neuronal cell markers in the neurospheres, possibly due to SPRY1 targeting by miR-21 in these cells, while miR-221 and miR-222 inhibition at the differentiated state reduced the expression of those differentiation markers. On the other hand, miR-29a and miR-29b targeted MCL1 in the GBM neurospheres and increased apoptotic cell death. Gene expression in differentiated cells relative to neurospheres in four different glioblastoma cultures

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2012-03-31 | E-GEOD-35306 | biostudies-arrayexpress

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