LncRNA DANCR suppresses differentiation of epithelial cells, however, its function in prostate cancer development is still unknown. In the present study, researchers at Xi’an Jiaotong University found the expression of DANCR increases in prostate cancer tissues and cells compared to normal prostate tissues and cells, moreover, DANCR promotes invasion and migration of prostate cancer cells in vitro and metastasis of tumor xenografts in nude mice. Mechanistically, they found that TIMP2/3, which are critical metastasis inhibitor of prostate cancer, were down-regulated by DANCR synergistically with EZH2 through epigenetically silencing their promoter by chromatin immunoprecipitation assay. In addition, the researchers further investigated whether DANCR is regulated by the differentiation-promoting androgen-androgen receptor (AR) pathway and found that DANCR expression is repressed by androgen-AR; furthermore, DANCR impedes the upregulation of TIMP2/3 and the suppression of invasion and migration by androgen-AR. On the other hand, interestingly, they found that in prostate cancer cells DANCR knockdown decreased the promotion of invasion and migration by the treatment of enzalutamide, which is an AR inhibitor.
Knockdown of DANCR decreases migration and invasion of prostate cancer cells
(A, B) C4-2B or CW22RV1 were transfected with indicated shRNA. The relative expression of DANCR were examined by RT-qPCR and normalized to GAPDH expression. The result expressed as the mean-SD, P < 0.05. (C, D) Knockdown of DANCR decreases migration and invasion of C4-2B or CW22Rv1cells, as detected by transwell assay. (E, F) Knockdown of DANCR decreases cell migration of C4-2B or CW22RV1 cells, as detected by wound healing assay. These results show data from at least three independent experiments, expressed as the mean ± SD. Representative figure of each experiment are shown at left.
These results indicate that DANCR promotes prostate cancer invasion and metastasis through repressing the expression of TIMP2/3, and suggest that DANCR could be a potential target for preventing prostate cancer metastasis, and knockdown DANCR may lessen the potential side effect of AR inhibitor.