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

Autor: Sevan Omer Majed, Suhad Asad Mustafa
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Small RNA
Turkey
Dishevelled Proteins
Gene Expression
Pathogenesis
Synaptotagmins
0302 clinical medicine
Breast cancer
Gene expression
Breast
Protein Phosphatase 2
RNA
Neoplasm
Cyclic AMP Response Element-Binding Protein
RC254-282
Reverse Transcriptase Polymerase Chain Reaction
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Oncology
030220 oncology & carcinogenesis
Female
Adult
Adolescent
Down-Regulation
miR-1275 and its target genes
Breast Neoplasms
Biology
03 medical and health sciences
Young Adult
microRNA
Genetics
medicine
Biomarkers
Tumor
Humans
Gene
miRNA
Aged
Gene Library
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Sequence Analysis
RNA
Research
Gene Expression Profiling
Tumor Suppressor Proteins
RNA
Cancer
medicine.disease
PRKACA
Biomarker (cell)
ADAM Proteins
MicroRNAs
030104 developmental biology
Small RNA and gene expression
Cancer research
And tumor suppressor
Zdroj: BMC Cancer
BMC Cancer, Vol 21, Iss 1, Pp 1-13 (2021)
ISSN: 1471-2407
Popis: Introduction 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.
Databáze: OpenAIRE
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