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Molecular pathogenesis of breast cancer: impact of miR-99a-5p and miR-99a-3p regulation on oncogenic genes.
- Source :
-
Journal of human genetics [J Hum Genet] 2021 May; Vol. 66 (5), pp. 519-534. Date of Electronic Publication: 2020 Nov 12. - Publication Year :
- 2021
-
Abstract
- Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.
- Subjects :
- Aminopyridines administration & dosage
Aminopyridines therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Benzimidazoles administration & dosage
Benzimidazoles therapeutic use
Breast Neoplasms drug therapy
Breast Neoplasms mortality
Breast Neoplasms pathology
Cell Line, Tumor
Down-Regulation
Female
Genes, erbB-2
Humans
Intracellular Signaling Peptides and Proteins biosynthesis
Intracellular Signaling Peptides and Proteins physiology
Kaplan-Meier Estimate
MicroRNAs physiology
Middle Aged
Neoplasm Proteins biosynthesis
Neoplasm Proteins physiology
Neoplasms, Hormone-Dependent drug therapy
Neoplasms, Hormone-Dependent mortality
Neoplasms, Hormone-Dependent pathology
Nuclear Proteins biosynthesis
Nuclear Proteins physiology
Piperazines administration & dosage
Piperazines therapeutic use
Prognosis
Progression-Free Survival
Pyridines administration & dosage
Pyridines therapeutic use
RNA Interference
RNA, Neoplasm physiology
RNA, Small Interfering genetics
Treatment Outcome
Breast Neoplasms genetics
Estrogens
Gene Expression Regulation, Neoplastic genetics
Genes, Tumor Suppressor
Intracellular Signaling Peptides and Proteins genetics
MicroRNAs genetics
Neoplasm Proteins genetics
Neoplasms, Hormone-Dependent genetics
Nuclear Proteins genetics
Oncogenes
Progesterone
RNA, Neoplasm genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1435-232X
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 33177704
- Full Text :
- https://doi.org/10.1038/s10038-020-00865-y