Abstract
Non-SMC condensin II complex subunit D3 (NCAPD3) is a subunit of the non-structural maintenance of chromosomes condensin II complex, which involves chromosome condensation and segregation during mitosis. NCAPD3 has recently been demonstrated as a crucial oncogenic factor. However, the underlying mechanism of NCAPD3 in prostate cancer (PCa) remains not completely clear. In this study, we confirmed that lncRNA MALAT1 was induced by NCAPD3-STAT3, and the expression of miR-30a-5p was controlled by NCAPD3 in PCa cells by miRNA-seq. Through quantitative real-time PCR, fluorescence in situ hybridization, western blotting, and immunohistochemistry assay, we demonstrated that miR-30a-5p was lowly expressed in PCa cells and tissues compared to the controls, which was contrary to NCAPD3 expression and markedly downregulated by NCAPD3. Then, MALAT1 was analyzed for the complementary sequence in the potential interaction with miR-30a-5p by using the predicted target module of public databases. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to verify that MALAT1 functioned as a sponge for miR-30a-5p to reduce miR-30a-5p expression. Meanwhile, MYC acted as a transcriptional repressor to directly bind the promoter of the miR-30a-5p located gene and repress the miR-30a-5p expression. Furthermore, the upregulation of NCAPD3 on cell viability and migration was significantly attenuated in PC-3 cells when miR-30a-5p was overexpressed. NCAPD3 overexpression also accelerated tumor growth in the xenograft mouse model and repressed miR-30-5p. In summary, this work elucidates NCAPD3 inhibits miR-30a-5p through two pathways: increasing STAT3-MALAT1 to sponge miR-30a-5p and increasing MYC to directly inhibit miR-30a-5p transcription, which could serve as potential therapeutic targets for prostate cancer.