The Study Of The Effect Of MALT1 On The Biological Behavior Of Human Prostate Carcinoma Cell Line

Objective: To investigate the role of MALT1 in the biological behaviors of prostate cancer cells,including proliferation,growth,apoptosis,invasion and migration and subcutaneous tumor proliferation ability in nude mice,respectively,Methods: The differential expression of MALT1 in prostate cancer cell lines LNCa P,PC-3,DU145,and the prostate cell line RWPE-1 was detected by q RT-PCR(Quantitative real time PCR)and Western blot.Short-hairpin RNA targeting MALT1 expressed in recombinant lentivirus were constructed(sh MALT1),and nonspecific sh RNA was used as negative control(sh Ctrl).Human PC-3 and LNCa P cells was transfected by sh MALT1 and sh Ctrl vectors,and they were control and experimental group,respectively.MALT1 expression levels were analyzed by q RT–PCR and Western blot in both groups,separately.Plate cloning experiment,MTT assay,flow cytometry cell apoptosis assay,Transwell migration and invasion assays were performed to investigate the effects of MALT1 on the ability of proliferation,growth,apoptosis,migration and invasion ability in prostate cancer.The nude mice were raised in SPF environment,xenograft models were constructed using LNCa P cells transfected by sh Ctrl and sh MALT1.After the subcutaneous implantation of cells,the animals were observed daily for tumour growth and subcutaneous tumours were measured on days 7,10,14,17,21,24,28,and 31.The nude mice were killed on the 31 th day,the tumor was dissected and weighed and part of the tissue was taken for immunohistochemistry assessment to evaluate Ki-67 expression in xenograft tumor tissues.Results: The result of q RT-PCR and Western blot indicated that MALT1 expression in a variety of prostate cancer cell lines were significantly higher than that of prostate urothelial cell line RWPE-1(P < 0.001).The expression of MALT1 in the MALT1 knockdown(sh MALT1)group was significantly lower than that of the negative control(sh Ctrl)group after knocking down MALT1 in LNCa P and PC-3 cell lines(P < 0.01).In sh MALT1 group,we found that the proliferation,growth,migration and invasion abilities of the two prostate cancer cell lines were significantly inhibited,furthermore,the apoptosis ratio was significantly increased(P < 0.05).The results of nude mice xenograft model proved that the tumorgenicity of LNCa P cells was reduced after MALT1 knockdown(P < 0.001).Furthermore,immunohistochemistry assessment showed that knockdown of MALT1 repressed the expression of proliferation marker Ki-67 in tumor tissues(P < 0.001).Conclusions: Inhibition of MALT1 attenuated prostate cancer cell proliferation,tumor growth,migration and invasion and promote cellular apoptosis in vitro.The vivo experiments also revealed that MALT1 knockdown suppressed tumorigenesis.These results suggest that MALT1 functions as an oncogene in prostate cancer,and may be a novel molecular target for prostate cancer therapy.