Signature microRNAs of nuclear Sm complex associated with breast cancer tumorigenesis.

It is well known that Sm proteins, small nuclear ribonucleoproteins, act as core spliceosomal factors in alternative splicing of mRNA precursors. MicroRNAs (miRNAs) can function in alternative splicing by targeting mRNAs of splicing factors. However, the direct interaction between miRNAs and proteins of splicing complex in nucleus has not been explored. In this study, the mature miRNAs in nuclear Sm complex of breast cancer cells and normal breast epithelial cells were characterized. Small RNA sequencing of immunoprecipitated nuclear Sm complex with the SmD1-specific antibody identified 123 and 170 mature miRNAs in nuclear Sm complex of normal breast cells and breast cancer cells, respectively. The results of Northern blot analysis confirmed the existence of mature miRNAs in Sm complex and electrophoretic mobility shift assay (EMSA) validated the binding of miRNAs with proteins of Sm complex. Among the identified miRNAs bound to the Sm complex in nucleus, 94 miRNAs were significantly upregulated, and 39 miRNAs significantly downregulated in breast cancer cells compared with normal breast cells, suggesting that miRNAs in nuclear Sm complex might be associated to tumorigenesis of breast cancer by regulating Sm complex during alternative splicing of mRNA precursors. Our study provided novel clues to reveal the regulatory mechanism of Sm complex in the assembly of spliceosome and contributed novel aspects of miRNAs to tumorigenesis of breast cancer.