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Disruption of cellular processes in the breast by abnormally expressed miRNA is characterized to develop cancer. We aimed to identify the differential expression of small RNAs (sRNAs) and mRNAs in formalin-fixed paraffin-embedded (FFPE) tissue of the breast cancer (BC) and normal adjacent tissue (NAT). Another aim is to determine the differential expression of  miR-1275  as a novel biomarker for BC and also identify its target genes.    Methods  TrueQuant method for analysis of sRNA expression and MACE-sequencing method for analysis of gene expression were used analyzing. The RT-qPCR technique was used to confirm  miR-1275  down expression. Target genes of  miR-1275  were computationally identified using target prediction sites and also the expression level of them was experimentally determined among the expressed genes.    Results  TrueQuant findings showed that 1400 sRNAs were differentially expressed in the FFPE tissue of two Kurdish cases with BC, as compared to NAT. Among the sRNAs, 29 small RNAs were shown to be significantly downregulated in BC cells. The RT-qPCR results confirmed that  miR-1275  was significantly down-expressed in 20 Kurdish cases with BC compared to NAT. However, Overall survival (OS) analysis revealed that the correlation between the expression level of  miR-1275  and clinical significance was highly corrected in cases with BC (OS rate:  P  = 0.0401). The MACE-seq results revealed that 26,843 genes were differentially expressed in the BC tissue compared to NAT, but 7041 genes were displayed in a scatter plot. Furthermore, putative target genes ( DVL3 ,  PPP2R2D ,  THSD4 ,  CREB1 ,  SYT7 , and  PRKACA ) were computationally identified as direct targets of  miR-1275  in several target predicted sites. The MACE-seq results revealed that the expression level of these targets was increased in BC tissue compared to NAT. The level of these targets was negatively associated with  miR-1275  expression. Finally, the role of down-regulated  miR-1275  on its targets in biological mechanisms of BC cells was identified; including cell growth, proliferation, movement, invasion, metastasis, and apoptosis.    Conclusion  Down-expressed  miR-1275 , a tumor suppressor, is a novel biomarker for early detection of BC.  DVL3 ,  PPP2R2D ,  THSD4 ,  CREB1 ,  SYT7 , and  PRKACA  are newly identified to be targeted by  miR-1275 .

MACE-Seq-based coding RNA and TrueQuant-based small RNA profile in breast cancer: tumor-suppressive miRNA-1275 identified as a novel marker