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HOX genes: potential candidates furthering the development of larynx squamous cell carcinoma.

ABSTRACT: Larynx squamous cell carcinoma (LSCC) is the second most aggressive cancer from head and neck (HSCC). Survival of LSCC patients has been found worsening, albeit significant advances in technology and therapeutics were made. We sought to clarify new genetic targets driven the development of LSCC. Analyzing tumors revealed that eight members of the homeobox gene family (HOX) were expressed 200 times more in LSCC samples than in normal larynx tissue. qPCR analysis validated all transcriptomic findings for the HOX gene family. Receiver Operating Characteristic statistical method (ROC curve) predicted that 8 members of the HOX gene family differentiate tumors from their normal surrounding tissue. Enabling the comparison of patient clinics with gene expression data, ROC curve analysis yet revealed that HOXC8 and HOXD11 genes are related to the tumor differentiation degree and regional lymph node metastasis, respectively. From siRNA assay, we found that HOXC8 and HOXD11 genes are essential for the expansion of FADU cell colonies. Our findings strongly suggest that members of the HOX family might be associated with the development of LSCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE59102 | GEO | 2014/12/25

SECONDARY ACCESSION(S): PRJNA254422

REPOSITORIES: GEO

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Project description:Adipogenesis occurs through a specific gene program in undifferentiated fat progenitors. We hypothesized that the properties of the fat progenitors are regulated by hox genes, the developmental genes essential in different tissue stem cells. Their biased expression in white and brown fat implies roles in distinguishing the two fat types. Among 39 Hox genes, Hoxc8 is highly enriched in undifferentiated adipose tissue stem cells (ADSCs) and down-regulated in differentiated adipocytes. Forced expression of Hoxc8 suppressed adipocyte differentiation of ADSCs. Using microarrays, we investigated the effect of Hoxc8 overexpression on global transcripts in ADSCs. We compared among four groups: untreated ADSCs, adipogenic induction media (MDI)-treated ADSCs, MDI-treated ADSC-vector and MDI-treated ADSC-Hoxc8. A number of, but not all, adipogenesis-related genes are suppressed by Hoxc8. This dataset illustrates the global effect of Hoxc8, a developmental transcription factor, on the expression of adipogenesis-related genes. Gene expression was compared among untreated ADSCs (control), adipogenic induction media-treated ADSCs, adipogenic induction media-treated ADSC-vector (ADSCs transduced with control vector), and adipogenic induction media-treated ADSC-Hoxc8 (ADSCs transduced with human Hoxc8). Total RNA was isolated from ADSCs using the Qiagen RNeasy kit (Qiagen). At NimbleGen, quality and yield were verified before cDNA synthesis and Cy3-end labeling. The labeled cDNA samples were hybridized to Homo sapiens 4-Plex arrays (Roche NimbleGen, A4487001-00-01) that represent 24,000 human genes. Raw data files for each sample were normalized and background-corrected using a Robust Multi-Array Analysis as implemented by NimbleScan software. Students’ two-tail t-tests were conducted among the samples for each transcript and fold-change was determined. Transcripts whose abundance was significantly altered (P < 0.05) and an absolute fold change greater than 2 were defined as differentially regulated.

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HOX genes: potential candidates furthering the development of larynx squamous cell carcinoma.

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