Expression and its clinical significance of tumor necrosis factor-α-induced protein-8 like-3 in colonic mucosa of patients with colon cancer / 中华消化杂志

Objective To detect the expression of tumor necrosis factor-α-induced protein-8 like-3 (TIPE3) in colonic mucosa of patients with colon cancer,and to analyze the correlation between its abnormal expression and clinicopathological features of patients with colon cancer.Methods The expression of TIPE3 mRNA in 58 cases of colon cancer and tumor adjacent tissues was detected by realtime polymerase chain reaction (RT-PCR).The expression of TIPE3 at protein level in 83 cases of colon cancer and tumor-adjacent tissues was determined by SP immunohistochemistry.Nonparametric rank-sum test and chi-square test were performed for statistical analysis.Results The relative expression of TIPE3 mRNA in the colon cancer tissues was 0.719 (0.104 to 0.887),which was lower than that of tumor-adjacent tissues (4.770,1.732 to 6.800),and the difference was statistically significant (Z=-6.345,P＜0.05).There was no statistically significant difference in the expression of TIPE3 mRNA in colon cancer tissues between different gender,age and TNM stage (all P＞0.05).The expression of TIPE3 mRNA in group of patients with lymph node metastasis (0.113,0.061 to 0.375) was lower than group of patients without lymph node metastasis (0.489,0.327 to 0.956;Z=3.815,P＜0.01).The expression of TIPE3 mRNA of patients survived less than five years after operation (0.104,0.049 to 0.220) was lower than that of patients survived over five years (0.482,0.266 to 0.908;Z=-3.653,P＜0.01).The expression of TIPE3 mRNA of patients with recurrence after operation (0.188,0.091 to 0.493) was lower than that of patients without recurrence (0.409,0.233 to 1.010;Z=-2.431,P=0.015).The recurrence rate of TIPE3 mRNA high expression group in five years after operation was lower than that of TIPE3 mRNA low expression group (23.1％,6/26 vs 56.2％,18/32);and the difference was statistically significant (x2 =6.508,P＜0.05).The expression of TIPE3 at protein level of colon cancer tissues (44.6 ％,37/83) was lower than that of tumor-adjacent tissues (68.7 ％,57/83;x2 =8.004,P＜0.05).The expression of TIPE3 at protein level was not correlated with age and gender (both P＞0.05).The positive expression rate of patients at stage Ⅱ was higher than that of patients at stage Ⅲ (60.5％,23/38 vs 29.7％,1/37);and the difference was statistically significant (x2 =7.174,P＜ 0.05).The positive expression rate of TIPE3 in group of patients with lymph node metastasis was lower than that of groups of patients without lymph node metastasis (28.2％,11/39 vs 59.1％,26/44),and the difference was statistically significant (x2=7.983,P =0.005).Conclusions The expression of TIPE3 in colon cancer tissues is lower than that in tumor-adjacent tissues.Furthermore,it is correlated with lymph node metastasis,recurrence rate and survival rate.TIPE3 may be involved in the genesis,development,invasion and metastasis of colon cancer.

Effect and mechanism of TIPE3 interference plasmid on SW480 colorectal canc-er growth / 中国免疫学杂志

Objective:To study the effect of interference TIPE3 on the colon cancer cell growth by transfecting SW480 colon cancer cells with the TIPE3 interference plasmid were detected.Methods:Transfecting the constructed TIPE3-shRNA-pSIREN-RetroQ plasmid to SW480 cells.To determine the highest interference efficiency plasmid ,the mRNA and protein levels of recombined plasmid were detected by RT-PCR and Western blot separately and tested the cell proliferation with CCK 8.Meanwhile,apoptosis rate of SW480 cells was determined by flow cytometry assay with AnnexinV-FITC/PI.To further determined the effects of recombined plasmid on cell development ,the level of protein involved in proliferation and apoptosis were detected by Western blot .Results:The most effecient in-terference plasmids were successfully constructed.We found that the cell survival rate decreased when interference TIPE 3 gene express-ing in colorectal cancer cells .Flow cytometry indicated that interefering the expression of TIPE 3 would increase the sensitivity of SW 480 cell to apoptosis induced by aDR5ScFv.The results of Western blot showed that low expression of TIPE 3 would activate caspase3 and downregulate the expression of p-AKT,p-PDK1 and PCNA.Conclusion:Interference TIPE3 could promote apoptosis and inhibit prolif-eration in SW480 colon cancer cells .

TIPE family:biological activities and functions / 中国免疫学杂志

The TIPE( tumor necrosis factor-alpha-induced protein 8-like) family has been recently described as regulators of tu-morigenesis and inflammation .The family consists of four highly homologous members: TNFAIP8 ( tumor necrosis factor-α-induced protein 8), TIPE1 (TNFAIP8L1), TIPE2 (TNFAIP8L2) and TIPE3 (TNFAIP8L3).Although TNFAIP8 family share high degrees of sequence homology , the members have different histological expressions , biological functions and molecular targets .TNFAIP8 shows the functions of inhibiting bacterial infection and promoting tumor migration .As a negative regulator of immunity and inflammation , TIPE2 is also an inhibitor of the oncogenic Ras in some neoplastic diseases .TIPE1 can induce cell apoptosis and inhibit tumor .TIPE3 is the transfer protein of phosphoinositide second messengers and can promote cancer .Emerging studies show TIPE family play important regulatory roles in many diseases;however, specific biological activities and exact molecular mechanisms need to be further elucidated .