Spliceosomal Associated microRNAs Signify Breast Cancer Cells: The Case of miR-7704

MicroRNAs (miRNAs) act as negative regulators of gene expression in the cytoplasm. Previous studies identified miRNAs in the nucleus. Here we study three breast-derived cell-lines (MCF-10A, MCF-7 and MDA-MB-231) and compared their miRNA sequences at the spliceosome fraction (SF). We report that the SF-miRNAs expression, identity, and pre-miRNA segmental composition are cell-line specific. The expression of the majority of the abundant SF-miRNAs (e.g. miR-100, miR-30a, and let-7 members) differs from that reported in the literature and in large cohorts of breast cancer patients, suggesting that nuclear miRNAs act on targets that are different from those of the cytoplasm. One such miRNA is miR-7704 whose genomic position overlaps HAGLR, a cancer-related lncRNA. We found an inverse expression of miR-7704 and HAGLR in the tested cell lines. Moreover, inhibition of miR-7704 caused an increase in HAGLR expression. Furthermore, elevated levels of miR-7704 attenuated the MDA-MB-231 cell-division rate., Altogether, we show that miR-7704 acts as a tumor-suppressor gene with HAGLR being its nuclear target in the SF. Altogether, we report on the potential of SF-miRNAs as an unexplored route for cancerous cell state.