IntroductionDisruption of cellular processes in the breast by abnormally expressed miRNA is characterized to develop cancer. We aimed to determine the differential expression of coding and non-coding RNAs in formalin fixed paraffin embedded (FFPE) blocks of breast cancer (BC) tissue and normal adjacent tissue (NAT). Another aim is to determine differential expression of has-miR-1275 as novel biomarker for BC and identify its target genes using prediction sites and experimentally expression level of them via the MACE-sequencing technique. MethodsMACE-sequencing technique was utilized to analyze differential expression of coding RNAs and small RNAs (sRNAs). Among small RNAs, miRNA-1275 expression was focused and confirmed using RT-qPCR technique in 20 Kurdish cases with BC . Moreover, clinical significance of miR- 1275 and its target genes was studied in a large number of patients with BC using the data obtained from The Cancer Genome Atlas database.ResultsThe MACE-seq findings showed that 1400 sRNAs and 26843 coding RNAs were differentially expressed in FFPE of BC tissue compared to NAT. Among these sRNAs, miRNA-1275 expression was found to be decreased in BC tissue compared to NAT. The decreased expression level of which was then confirmed via RT-qPCR technique to farther prove in 20 Kurdish cases with BC . Furthermore, the correlation between the expression level of miRNA-1275 and clinical data were evaluated to be highly corrected in cases with BC (overall survival rate: P = 0.0401). However, putative target genes ( DVL3, PPP 2R2D, THSD4, CREB1, SYT7, and PRKACA) were computationally identified as direct targets of miRNA-1275 in several target predicted sites. Among coding RNAs, the expression level of these targets was increased in BC tissue compared to NAT. The levels of these targets were negatively associated with miRNA-1275 expression. Finally, the role of down-expressed miRNA-1275 and its targets in BC cells were identified to attenuated biological mechanisms; including cell growth, proliferation, movement, invasion, metastasis, and apoptosis.Conclusiondown-expressed miR-1275 , a tumor suppressor, is as a novel biomarker for early detection of breast cancer. DVL3, PPP 2R2D, THSD4, CREB1, SYT7, and PRKACA are novely identified to be targeted by miR-1275 in BC cells.