onji Domain Containing 1A Is a Novel Prognostic Marker Colorectal Cancer: In vivo Identification from R oxic Tumor Cells

ownloade pose: This study aimed to identify novel hypoxia-inducible and prognostic markers in vivo from ic tumor cells. erimental Design: Using carbonic anhydrase 9 and CD34 as a guide for hypoxic tumor cells, laser e microdissection was used to isolate colorectal cancer (CRC) liver metastases. The samples were ed by microarray analysis, in parallel with five CRC cell lines cultured under hypoxic conditions. To te the prognostic impact of the expression of certain genes, samples from a total of 356 CRC pawere analyzed by microarray or quantitative reverse transcription-PCR. In vitro mechanistic studies vivo therapeutic experiments were also done about a histone H3 Lys demethylase, Jumonji docontaining 1A (JMJD1A). ults: Several candidate genes were identified by microarray analysis of liver metastases and culturCRC cells under hypoxic conditions. Among them, we found that JMJD1A was a novel independent ostic factor for CRC (P = 0.013). In vitro assays revealed that loss of JMJD1A by small interfering reatment was associated with a reduction of proliferative activity and decrease in invasion of CRC nes. Furthermore, treatment with an adenovirus system for antisense JMJD1A construct displayed inent therapeutic effects when injected into established tumor xenografts of the CRC cell lines 16 and DLD1. HCT1 Conclusions: JMJD1A is a useful biomarker for hypoxic tumor cells and a prognostic marker that could be a promising therapeutic target against CRC. Clin Cancer Res; 16(18); 4636–46. ©2010 AACR.

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