| Background:Colorectal cancer (CRC) is one of the most common types of malignant tumors with a high mortality and morbidity. It’s necessary to find out reliable molecular biomarkers to predict the prognosis of this tumor. Protein arginine methyltransferase1(PRMT1) is the first coloned protein among protein arginine methyltransferases family, and previous works have shown that protein arginine methyltransferase1(PRMTl) is over-expressed in many tumors, especially in breast cancer, bladder cancer, leukemia and so on, but the expression of PRMT1in CRC and its clinical significance is not clear.Objective:To detect the expression of PRMT1in colorectal caner, and analyze the association with clinicopathologic data and prognosis to identify whether PRMT1protein could be used as a prognostic marker in patients with CRC. Then to investigate whether knockdown of PRMT1expression could influence the biologic behaviors (proliferation, apoptosis and migration) of colon cancer cells.Methods:The expression of PRMT1protein in298CRC tissues and the paired170tissue samples were detected by immunohistochemical (IHC) staining and western blot. All the patients were followed up, and their clinicalpathological characteristics were correlated with the PRMT1expression and analyzed with univariate and multivariate statistic analysis. Kaplan-Meier and Cox regression were used for survival analysis. The expression of PRMT1in8colorectal cancer cell lines was detected by western blot and real-time PCR. To examine the role of PRMT1in proliferation, apoptosis and migration of colon cancer cell lines, the sequences of specifical StealthTM RNAi directed at PRMT1were synthetized and transfected with three colon cancer cells. After that, MTT assay, clone formation, flow cytometer, Annexin V-PI double staining test, scratch test and Transwell test were done in the three colon cancer cells.Results:The expression rate of PRMT1protein in the sporadic CRC (81.5%) was significantly higher than the paired control group (27.1%, P=1.94×10-31). The expression of PRMT1protein in CRC tissue was significantly associated with the diameter of the tumor, the expression rate were87.0%for tumor≥5cm and11.1%for tumor<5cm (Chi-squire P=0.042, Logistic regression P=0.032). PRMT1protein expression might be associated with the clinical stage, the expression rate elevated from I stage to IV stage tumors (Chi-squire P=0.159, Logistic regression P=0.037). Those patients who had lyphnode metastastis pre-surgery had a higher expression (86.1%) than those who had no lyphnode metastasis (77.6%)(Chi-squire P=0.060, Logistic regression P=0.047). The expression of PRMT1protein could lead to a decrease of the survival rate (P=0.087), and Cox regression revealed that PRMT1protein might be an independent predictor of the prognosis of CRC patients, although there was no obviouse statistical significance (P=0.107).Then MTT assay and clone formation results indicated that knockdown of PRMT1would slow down the speed of colon cancer cells proliferation abilities, block the G1phase to S phase in cell cycle, wound-healing assay and Transwell test showed that down-regulation of PRMT1expression could impede the migratory ability of colon cancer cells. Knockdown of PRMT1only increased the ratio of apoptosis loVo colon cancer cell.Conclusions:The expression of PRMT1protein was higher in CRC tissues than in normal colorectal tissues.The expression of PRMT1protein was notably correlated with the size of the tumor and might correlate with metastasis of lyphnode and a poor survival of CRC patients.Knockdown of PRMT1expression could influence the biologic behaviors of colon cancer cells, especially proliferation and migration. PRMT1protein might be a new prognostic bio-marker for CRC patients. |
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