The Role Of Three Ubiquitin Ligases In Colorectal Carcinoma

E3 ubiquitin ligases play important role in several cancers.In this study,we aim to explore the role of three ubiquitin ligases TRIM46,TRIM55 and RNF6 in colorectal carcinoma.CCK-8 cell proliferation and transwell cell invasion assay were implemented to observe the effect of TRIM46 on proliferation and invasion in HCT116 cells.Western blot was performed to study the protein expression of SHP1.The data showed that knockdown of TRIM46 significantly suppressed cells proliferation and invasion in HCT116 cells,and the expression of SHP1 was increased.Real time PCR was performed to examine the expression level of TRIM55 in 70 specimens of colorectal cancer and the paired adjacent tissues.Cell Counting Kit-8 was used to explore the proliferation ability in HCT116 cells after TRIM55 siRNAs transfection.Western blot was implemented to observe the effect of TRIM55 down-regulation on SOCS1.The expression of TRIM55 was significantly increased in 49 CRC patients' tissues,compared with paired adjacent tissues.The level of TRIM55 was dramatically associated with tumor differentiation,AJCC stage and lymph node metastasis.Knockdown of TRIM55 impaired the proliferation ability of HCT116 cells and increased the protein level of SOCS1.To explore the role and molecular mechanisms of RNF6 in colorectal cancer,the expression of RNF6 in the specimens of colorectal cancer and the paired adjacent tissues was examined.Cell Counting Kit-8 and nude mice xenograft were used to explore the proliferation ability of colorectal cancer cells with RNF6 knockdown.Transwell cell invasion assay was implemented to observe the effect of RNF6 on invasion in colorectal cancer cells.Western blot and Co-IP were performed to explore the mechanisms.The proliferation and invasion ability of colorectal cancer cells were promoted in response to RNF6 up-regulation.RNF6 may interact with SHP1,indicating that RNF6 exerted the oncogene role through the ubiquitination and degradation of SHP1.