Abnormal expression of APRIL in colorectal cancer cells promotes tumor growth and metastasis

Objective To investigate the effects of a proliferation-inducing ligand (APRIL) on colorectal cancer (CRC) cell growth and migration,and to observe the role of APRIL in CRC biological behavior.Methods The siRNA plasmid vector targeting APRIL gene (APRIL-siRNA) was transfected into human colorectal cancer SW480 cells and recombinant human APRIL (rhAPRIL) was used to stimulate human colorectal cancer HCT-116 cells.Cell proliferation activity was analyzed using cell counting kit-8 (CCK-8),cell cycle was detected by flow cytometry,and the protein expression of cyclin D1,p21 and Bcl-2 was detected by Western blot analysis.Tumor cell migration and invasion were measured by Transwell chambers.RT-PCR was applied to examine the mRNA expression level of MMP-2 and MMP-9.APRIL-siRNA was used to transfect directly SW480 cells,which were injected subcutaneously into nude mice,then the tumor growth and metastasis were observed.Results Cell proliferation ability of APRIL-siRNA-transfected SW480 cells was drastically repressed,and the percentage of G0/G1 phase cells was significantly increased (t =4.12,P ＜ 0.05),accompanied with depressed cyclin D1,Bcl-2 expression and elevated p21 expression.Cell proliferation ability of rhAPRIL-stimulated HCT-116 cells was promoted with a decreased G0/G1 phase ratio (t =3.31,P ＜ 0.05).cyclin D1 and Bcl-2 protein expression was up-regulated while p21 was down-regulated by rhAPRIL stimulation.Metastatic and invasive capacities of APRIL-siRNA-transfected SW480 cells were significantly inhibited compared with their respective controls (both P ＜ 0.05),accompanied with the deregulated MMP-2 and MMP-9 mRNA expression.Metastatic and invasive capacities of rhAPRIL-stimulated HCT-116 cells were promoted with up-regulated MMP-2 and MMP-9 mRNA expression(both P ＜ 0.05).Tumor growth in the group transfected with APRIL-siRNA appeared to be slower than that in the control groups and the expression of MMP-2,MMP-9 in tumor tissues was depressed in the APRIL-siRNA group.Conclusions APRIL facilitates tumor growth and metastasis,and is associated with carcinogenesis and prognosis.Our findings suggest that APRIL might be used as a novel target for the intervention and therapy of colorectal cancer. Key words: Colorectal neoplasms;  Cell proliferation ;  Neoplasm metastasis;  A proliferation-inducing ligand ;  Prognosis