Regulation between two alternative splicing isoforms ZNF148^FL and ZNF148^ΔN, and their roles in the apoptosis and invasion of colorectal cancer.

OBJECTIVE:To investigate the effect of two alternative splicing isoforms of zinc finger protein (ZNF) 148 gene on the invasion and metastasis of human colorectal cancer (CRC) cells and their related mechanisms. METHODS:Quantitative RT-PCR assays were used to detect the expression of twoZNF148 alternative splicing isoforms in SW480 cells. ZNF148^FL-siRNA, ZNF148^FL-over express vector, ZNF148^ΔN-siRNA, and ZNF148^ΔN-over express vector were introduced into SW480 cells. The transfection efficiency was confirmed by RT-PCR. The proliferation, invasion, and migration in vitro as well as the apoptosis of SW480 cells were detected by MTT, transwell, scratch assay and flow cytometry, respectively. RESULTS:Both ZNF148^FL and ZNF148^ΔN were expressed in SW480 cells, and the level of ZNF148^FL protein was higher than ZNF148^ΔN. After ZNF148^FL-siRNA and ZNF148^ΔN-over express transfection, the expression level of ZNF148^FL and ZNF148Δ^N were significantly decreased and increased, respectively. In contrast, the expression of ZNF148^FL and ZNF148^ΔN were significantly increased and decreased, respectively, after ZNF148^FL-over express and ZNF148^ΔN-siRNA transfection (all P < 0.05). The proliferation of SW480 cells was increased in ZNF148^FL-over express group and the ZNF148^ΔN-siRNA group, while decreased in ZNF148^FL-siRNA group and ZNF148^ΔN-over express group. The invaded cell number and migrated distance in ZNF148^FL-siRNA group and ZNF148^ΔN-over express group were significantly decreased, but the apoptotic rate was significantly increased. In contrast, ZNF148^FL-over express and ZNF148^ΔN-siRNA group showed the significantly increased ability of invasion and migration but decreased apoptosis rate (all P < 0.05). CONCLUSION:ZNF148^FL could increase proliferation, invasion, and migration of CRC cells, while ZNF148^ΔN showed opposite effect; the two splicing isoforms of ZNF148 may exert a mutual antagonistic effect to each other on the malignant biological activities.

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