Studies On The Transcriptional Regulation Of C1orf10

Chromosome1open reading frame10（C1orf10） is located on chromosome1q21within the epidermal differentiation complex fused-gene family. C1orf10proteincontains two EF-hand Ca²⁺binding domains in its N-terminus and two glutamine-andthreonine-rich60amino acid repeats in its C-terminus. Our pervious study usingcDNA microarray showed that C1orf10is downregulated in esophageal squamouscell carcinoma （ESCC） tissues compared to its corresponding normal counterparts.C1orf10haplotypes containing–1747G/T,–1139G/C,–1079G/A,–900G/T,Gly480Ser, and4666G/A are significantly associated with susceptibility to ESCC.C1orf10, also known as squamous epithelial heat shock protein53（SEP53）, may playa role in the mucosal/epithelial immune response and epidermal differentiation.Moreover, C1orf10is involved in response to chemoradiosensitivity of esophagealcancer.In this study, we investigated the relationship between the C1orf10expression andclinicopathological parameters of ESCC, and studies on the transcriptional regulationof C1orf10. This study can be divided into three parts:1. To investigate the relationship between the C1orf10expression andclinicopathological parameters of ESCC, we analyze the expression of C1orf10in110paired ESCC tiusses using immunohistochemistry. C1orf10protein was mainlylocalized in the cell cytoplasm, and was downregulated in ESCC. Expression ofC1orf10was associated with cell differentiation using SPSS17.0. These resultsimplicated C1orf10as an important predictor of esophageal squamous celldifferentiation.2. To investigate the reason of C1orf10downregualted in ESCC, we examine thetranscriptional regulation of C1orf10. First, we found that C1orf10promoter regioncontains transcription factor AP-1, HSF and CEBP binding sites using bioinformaticanalysis. Secondly, we identfy the core promoter region of C1orf10（positions-492to+26） using luciferase reporter assay. Transcription factors of CEBP a、AP-1and HSFpositively regulate transcription of C1orf10, and can bind and activate C1orf10promoter in vivo using chromatin immunoprecipitation. Moreover, C1orf10 expression is correleated with the expression of transcription factor of AP-1、HSFand CEBP a in30paried ESCC tiusses.3. To identify C1orf10involved in DNA damage response, we assessedDNA-damaging agents such as cisplatin、taxol or ionizing radiation on C1orf10expression in KYSE30cells. C1orf10expression was induced in response to DNAdamage by Western blot. Simarly, transcription factors （AP-1and CEBP） was alsoinduced. These results indirectly indicate that the transcription factors of AP-1andCEBP may be involved in transcriptional regulation of C1orf10, suggesting thatC1orf10expression may be involved in the chemosensitivity of ESCC.Taken together, these results suggested that C1orf10were regulated by thetranscription factor AP-1、HSF1/2and CEBP in KYSE30cells. C1orf10wasinvolved in squamous epithelial cell differentiation and chemoradosenstivity ofESCC.