Research On The Effects Of SCIN Gene To The Signal Pathway Of Liver Metastasis Of Colorectal Cancer

Objective:By gene-chip technology, we search for those genes which differentially expressed with SCIN(Scinderin) in colorectal cell (In the earlier stage, our research in colon cancer patients with and without liver metastasis, showed that SCIN was the most differentially expressed gene between these two groups). By Real time-PCR, we verify these genes whether interact with SCIN or not. We review those genes interact with SCIN through bioinformatics analysis. Then we can find out the signal pathway that SCIN may lead to liver metastasis of colorectal cancer.Methods1. Based on earlier research result, by RNAi technology, we construct positive clones contain the RNAi-SCIN lentivirus vector. Using it to infect DLD1cell and measure the Lentivirus.2. Based on Agilen4x44high throughput expression profile gene-chip technology, we analyse DLD1cell(NC cell) and DLD1-RNAi-SCIN(KD cell) to search for differentially expressed genes. Consequently, we search for the possible interacted genes based on Gene Ontology and Pathway analysis(filtering criteria:|Fold Change|<2, P<0.05). Further more, by bioinformatics analysis, we find out those genes inteact with SCIN in the signal pathway lead to proliferation and invasion.3. By real-time PCR, we verify genes which are found out during the above research. The result shows genes interact with SCIN definitely. By bioinformatics analysis, we find out these genes interact with SCIN in the signal pathway which lead to colorectal cancer and liver metastasi. Finally, we can get the signal pathway SCIN plays a role in which lead to liver metastasis of colorectal cancer.Results1. Succeed in acquiring experimental cell. By gene-chip technology, we find952differentially expressed genes. Among them257expressed up and695expressed down. By bioinformatics analysis genes in the signal pathway lead to proliferation and invasion are CDKN2B、CDKN2C、CDK2、COL4A1、DIAPH1、PRKCA、 MCM4、CDK4、STAT3、CCNB1、EGFR、ARHGAP5、RAC1、ITGB1、DHFR and PLCB1.2. By real-time PCR, SCIN can raise these genes expression:DIAPH1、CDK2、 STAT3、CDK4, EGFR, and decrease CDKN2B and COL4A1expression.3. By bioinformatics analysis, we find COL4A1has nothing to do with colorectal cancer. CDK2、CDK4、CDKN2B、STAT3and DIAPH1can play each role in the development of colorectal cancer by its own signal pathway. Based on this we can confirm SCIN is closely related to colorectal cancer. ERBB signal pathway and PI3K-AKT signal pathway which EGFR relate to are closely related to colorectal liver metastasis. Therefore we consider SCIN leads to colorectal liver metastasis may be via EGFR related ERBB and PI3K-AKT signal pathway.Conclusion:SCIN gene is closely related to colorectal cancer and liver metastasis; SCIN leads to colorectal liver metastasis may via EGFR and PI3K-AKT signal pathway. SCIN may become the new potential target on colorectal liver metastasis therapy. Meanwhile SCIN can lead to the development of colorectal cancer via CDK2、CDK4、CDKN2B、 STAT3and DIAPH1.