Unknown,Transcriptomics,Genomics,Proteomics

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Microarray analysis of microRNA expression patterns in different hepatocellular cancinoma subtypes

ABSTRACT: Previously, we have found a specific subtype of HCCs named solitary large hepatocellular carcinoma (SLHCC), which was >5 cm in diameter, had just single lesion, and always grew expansively within an intact capsule or pseudocapsule. Accordingly, we classified HCCs into 3 different subtypes: SLHCC, nodular HCC (NHCC, node number ≥ 2) and small HCC (SHCC, solitary nodular, diameter ≤ 5 cm). Further study confirmed that SLHCC had unique clinical and pathological characteristics, and its metastatic potential was comparable with SHCC, but significantly lower than NHCC. After hepatic resection, SLHCC exhibited a similar long-term overall and disease-free survival with SHCC, but much better than NHCC. To gain a better understanding of the molecular biologic characteristics of SLHCC, we performed miRNAs array analysis in there three subtypes of HCC.

ORGANISM(S): Homo sapiens

SUBMITTER: Feng Fang

PROVIDER: E-MTAB-3347 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Chromosomal DNA copy number alterations are a hallmark of human malignancies, including hepatocellular carcinoma (HCC). However, which oncogenes or tumor suppressors located on regions with DNA copy number aberration may contribute to HCC initiation and progression still remain obscure. Here we performed a genome-wide DNA copy number analysis on human HCC samples to identify novel potential oncogenes or tumor suppressors with DNA copy number aberrations. Genome-wide DNA copy numbers analysis was performed with single nucleotide polymorphism micoarray. RT-PCR and immunohistochemical staining were employed to evaluate the NOXIN expression in HCC samples. Colony formation, cell cycle analysis and tumor xenograft assays were performed to assess the role of NOXIN in HCC cells. Reciprocal co-immunoprecipitation experiments were used to detect the interaction between NOXIN and DNA polymerase a primase. Genome-wide DNA copy number analysis on 43 paired HCC samples indentified the smallest DNA amplification region containing NOXIN, along with the elevated transcript. NOXIN overexpression was significantly associated with HCC tumor stage. Enforced NOXIN promoted cellular proliferation, colony formation, cell migration and in vivo tumorigenicity, whereas RNA interference against NOXIN can attenuate these effects. Interestingly, NOXIN overexpression can accelerate the G1-S transition of cell cycle progression through enhancing DNA synthesis in HCC cells, as indicated by bromodeoxyuridine incorporation. Furthermore, NOXIN can interact with DNA polymerase a, implying that NOXIN may promote de novo DNA synthesis via affiliating formation of DNA polymerase-primase complex. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from hepatocellular carcinoma and adjacent liver tissue samples. Copy number analysis of Affymetrix 500K SNP arrays was performed for 43 hepatocellular carcinoma tissue samples, which their adjacent liver tissues were used as references for copy number inference.

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Microarray analysis of microRNA expression patterns in different hepatocellular cancinoma subtypes

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