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Transcriptome analysis in tumor budding positive hepatocellular carcinoma tissue samples relative to tumor budding negative hepatocellular carcinoma tissue samples

ABSTRACT: Tumor budding (TB) has become a crucial factor for predicting the malignancy grade and prognostic outcome for multiple solid cancers.Studies have investigated the prognostic value of TB within hepatocellular carcinoma (HCC). However, its molecular mechanism within HCC remains unclear. This is the first study to discover and compare the expression of differentially expressed genes (DEGs) between TB-positive and TB-negative HCC tissues. Total RNA was extracted from 40 fresh HCC tissue samples with different TB statuses and then sequenced. This study provides insights into the possible mechanisms of TB in HCC and revealed potential predictive diagnosis markers and treatment targets for HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227335 | GEO | 2023/04/02

REPOSITORIES: GEO

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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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Transcriptome analysis in tumor budding positive hepatocellular carcinoma tissue samples relative to tumor budding negative hepatocellular carcinoma tissue samples

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