The Studies On The Differentially Expression Of HPRG2and TGF-β Signaling Pathway Members In Colorectal Cancer And Their Correlation

The morbidity of colorectal cancer is very high and it is still rising in recent years. In China, the mortality of colorectal cancer is the fourth malignancy, which seriously damaged human health. The incidence of colorectal cancer is closely associated with diet, environment, genetic.Multiple-stage of genes also involved in the pathogenesis, which is one of focuses in cancer research. Although some progresses were made in cancer pathology in recent years, the molecular mechanisms are far from clarified. Therefore, it is very important to explore the molecular mechanism of colorectal cancer, which might contribute to clarify the pathogenesis of colorectal cancer at molecular level, and use molecular genetics diagnosis and interventions to treat cancer ultimately.Many studies indicate that TGF-β signaling pathway plays an important role in the tumorigenesis, development and metastasis of tumors. A new gene HPRG2that might be a new member of TGF-P signaling pathway was identified from human cDNA library in our laboratory. It indicated that HPRG2was not only highly expressed in heart, but also expressed in intestine, kidney, liver by western-blot. HPRG2could interact with the TGF-β signaling pathway members Smad6and Smad7had verified by the co-immunoprecipitation. HPRG2partially inhibited the phosphorylation of Smad2/3, which stimulated by TGF-β, then inhibited the process that Smad4get into nuclear, it was detected by using a HPRG2overexpressioned stable cell line. The results suggest that HPRG2likely to participate in the TGF-P signaling pathway. The pre-works in our laboratory show that HPRG2has a different expression in variety cancers. The earlier results suggest that HPRG2is likely to regulate tumorigenesis of cancer through TGF-β signaling pathway. Nevertheless, the differentially expression and correlation analysis of HPRG2and TGF-β signaling pathway members in colorectal cancer are still not being reported.In order to study the differentially expression and correlation of HPRG2and TGF-β signaling pathway members in colorectal cancer, we used RT-PCR to detect the expression level of HPRG2and TGF-p signaling pathway members in the normal cell lines and cancer cell lines, and found that HPRG2and TGF-β signaling pathway members have similar expression patterns in different cell lines. Then it was verified that HPRG2has regulated the TGF-β signaling pathway members in a positive transcriptional way by using the HPRG2over expressed stable cell lines, and found they have a correlation expression pattern as well. We choose the colorectal cancer to further validate its regulatory mechanism, and expanded the sample numbers by two ways. Firstly, we screened29microarray data that meet the criterion using the public microarray databases, and discovered that HPRG2and TGF-β signaling pathway members Smad6, Tgf-β2and Smad2have an association. Secondly, we applied the colorectal cancer tissue samples for RT-PCR experiments, but found HPRG2and TGF-β signaling pathway members Smad4have an association. According to the two-way function of TGF-β signaling pathway in cancer, we divided the eight groups into HPRG2high expression groups and HPRG2low expression groups. Through analyzing the results, we found both groups showed the consistency upregulated and downregulated of the TGF-β signaling pathway members. It suggests that HPRG2may regulate the tumorigenesis of colorectal cancer through the TGF-β signaling pathway members at transcription level.In summary, this study speculated that the HPRG2may regulate the tumorigenesis of colorectal cancer through TGF-β signaling pathway members at transcription level through the tissue level, cellular level and a large number of microarray data. It provides clues for discovering the new therapeutic targets and developing new treatments of colorectal cancer.