CDK3, target of miR-4469, suppresses breast cancer metastasis via inhibiting Wnt/β-catenin pathway

Oncotarget. 2017 May 25;8(49):84917-84927. doi: 10.18632/oncotarget.18171. eCollection 2017 Oct 17.


Cyclin-dependent kinase 3 (CDK3), a member of CDK family, is involved in G0/G1 and G1/S cell cycle transitions. Although several researchers discovered that CDK3 related to cell growth in some kinds of cancer, the functions of CDK3 during tumor development remains unclear. Here, we first found that the expression of CDK3 was higher in primary tumors of non-metastatic breast cancer compared with those in metastatic breast cancer. Overexpression of CDK3 suppressed cell migration and invasion of breast cancer cells, and decreased the metastasis in nude mice. We further identified miR-4469 was a negative regulator of CDK3 by directly targeting its 3'-untranslated region (UTR). The increase of motility induced by miR-4469 could be abolished by CDK3 overexpression. Moreover, RNA-seq analysis revealed that Wnt pathway may be inhibited by CDK3 expression, which was subsequently confirmed by western blot. Moreover, Wnt3a treatment abolished the inhibitory role of CDK3 in cell motility, suggesting that Wnt signaling is the potential downstream of CDK3. In conclusion, these results support that CDK3 which is targeted by miR-4469 suppresses breast cancer metastasis by inhibiting Wnt/β-catenin pathway.

Keywords: CDK3; Wnt pathway; breast cancer; metastasis; microRNA.