Project description:To validate that the aggregation pattern identifies a pro-tumoral Mφ subset in HCC, we have employed microarray expression profiling as a discovery platform to identify the molecular and functional implications of Mφ spatial distribution in HCC. Gene ontology (GO) and gene-set enrichment analyses (GSEA) revealed that tissues rich in aggregated Mφs significantly upregulated tissue remodeling pathways and “M2” Mφ-associated genes, while pro-inflammatory “M1” gene sets were more pronounced in HCCs with predominantly scattered Mφs. These results indicate that Mφ aggregation signifies a transition to a multifaceted, pro-tumoral phenotype, highlighting the intricate relationship between spatial distribution and function of Mφs in the tumor milieu.
Project description:HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions. Using cell type–specific spatial transcriptomics techniques to separate cancer cells and endothelial cells applied to a set of 41 resected HCC tissue specimens, we report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner. Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous sig- naling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer- endothelial cell interactions and related drug targets.
Project description:RNA-sequencing of Human hepatocellular carcinoma (HCC) cells We analyzed two circRNA profiles expressed in human HCC tissues and identified circRHOT1 as a conserved and dramatically upregulated circRNA in HCC tissues. HCC patients displaying high circRHOT1 level possessed poor prognosis. We demonstrated circRHOT1 significantly promoted HCC growth and metastasis. In order to investigate the mechansim of circRHOT1, we constructed circRHOT1-deficient HCC cell lines. Through RNA-sequencing, we sough to identify the key gene regulated by circRHOT1 in HCC.
Project description:We evaluated the expression of known human miRNAs in human hepatocellular carcinoma (HCC) and normal hepatic tissues from southeast China, and identified the differentially expressed miRNAs in HCC tissues. We use microRNA array platform from CapitalBio Corp. to access the miRNA expression profiles in HCC and non-tumor liver samples from Southeast China. There were 5 HCC samples and 3 non-tumor liver samples in our study. As the microarray platform we used was based on a older version of miRBase, we mapped the probe sequences to a newer version of miRBase before these data was applied to further analysis.
Project description:In this study the generic impact of protein aggregation (aggregation of proteins not associated with neurodegenerative disease) on gene expression in cultured cells was investigated by DNA microarray technology. The survey of gene expression showed that the Hsp40, Hsp70 and Hsp105 genes, all of which have documented aggregation suppression activity, were up-regulated. Unexpectedly, the survey also showed increased expression of the MEK5 gene with concomitant silencing of the MEK3 gene. The expression pattern of MEK5 at the mRNA and protein levels aligns with the kinetics of aggregate formation and dissolution. Cell viability was unaffected by protein aggregates. These findings are of particular importance for chronic neurodegenerative diseases where the intraneuronal accumulation of aggregate-prone proteins are a major characteristic of the diseases. The identification of changes in MEK5 gene expression have been observed in Alzheimer-related diseases which provides new diagnostic and therapeutic avenues in these diseases. The molecular neuropathological findings would not have occurred without the generic microarray analyses.