WISP2/CCN5 gene knockdown in vitro and in vivo exhibits proliferation promotion of breast cancer through targeting Skp2 and p27Kip1

Background Emerging evidence has demonstrated that WISP2/CCN5 is critically involved in tumorigenesis. However, the function of WISP2/CCN5 in breast cancer carcinogenesis is largely unclear. Methods we aim to explore the effects and potential mechanisms of WISP2/CCN5 on proliferation of breast cancer cells and carcinogenesis of breast cancer xenograft. Lentivirus vector with WISP2/CCN5shRNA was transfected into MCF-7, and breast cancer cells and xenograft were conducted. Effect of WISP2/CCN5 on growth and carcinogenesis of breast cancer cells and xenografts was evaluated by MTT assay and tumor volume. The relationship between WISP2/CCN5, Skp2 and p27Kip1 was detected in vitro and in vivo by RT-PCR at mRNA level and Western blotting at protein level. Results The result of MTT assay indicated that MCF-7 cell growth viability in WISP2/CCN5 gene knockdown group was significantly higher than negative vector group( P <0.05) or control group ( P <0.05). It suggested that knockdown of WISP2/CCN5 gene by shRNA lentivirus plasmid promoted proliferation of MCF-7 cells. The growth curves of breast cancer xenograft showed that xenografts in WISP2/CCN5 knockdown group grew more quickly than negative vector group( P < 0.05) or control group ( P < 0.05). Subsequently, the results of RT-PCR and Western blotting revealed that WISP2/CCN5 gene knockdown led to increased Skp2 and decreased p27Kip1 at mRNA and protein levels. WISP2/CCN5 exerts its inhibition on proliferation of MCF-7 cell line and suppressive functions on growth of breast carcinoma via regulation of Skp2 and p27Kip1at mRNA and protein levels. However, WISP2/CCN5 gene knockdown resulted in loss of inhibition effect on MCF-7 and breast cancer. Conclusions Our findings suggest that WISP2/CCN5 could be a useful therapeutic strategy for the treatment of breast cancer through targeting Skp2 and p27Kip1.