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RNA-sequence-based microRNA expression signature in breast cancer: tumor-suppressive miR-101-5p regulates molecular pathogenesis
- Source :
- Molecular Oncology, Molecular Oncology, Vol 14, Iss 2, Pp 426-446 (2020)
- Publication Year :
- 2019
-
Abstract
- Aberrantly expressed microRNA (miRNA) are known to disrupt intracellular RNA networks in cancer cells. Exploring miRNA‐dependent molecular networks is a major challenge in cancer research. In this study, we performed RNA‐sequencing of breast cancer (BrCa) clinical specimens to identify tumor‐suppressive miRNA in BrCa. In total, 64 miRNA were identified as candidate tumor‐suppressive miRNA in BrCa cells. Analysis of our BrCa signature revealed that several miRNA duplexes (guide strand/passenger strand) derived from pre‐miRNA were downregulated in BrCa tissues (e.g. miR‐99a‐5p/‐3p, miR‐101‐5p/‐3p, miR‐126‐5p/‐3p, miR‐143‐5p/‐3p, and miR‐144‐5p/‐3p). Among these miRNA, we focused on miR‐101‐5p, the passenger strand of pre‐miR‐101, and investigated its tumor‐suppressive roles and oncogenic targets in BrCa cells. Low expression of miR‐101‐5p predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0316). Ectopic expression of miR‐101‐5p attenuated aggressive phenotypes, e.g. proliferation, migration, and invasion, in BrCa cells. Finally, we identified seven putative oncogenic genes (i.e. High Mobility Group Box 3, Epithelial splicing regulatory protein 1, GINS complex subunit 1 (GINS1), Tumor Protein D52, Serine/Arginine‐Rich Splicing Factor Kinase 1, Vang‐like protein 1, and Mago Homolog B) regulated by miR‐101‐5p in BrCa cells. The expression of these target genes was associated with the molecular pathogenesis of BrCa. Furthermore, we explored the oncogenic roles of GINS1, whose function had not been previously elucidated, in BrCa cells. Aberrant expression of GINS1 mRNA and protein was observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126). Knockdown of GINS1 inhibited the malignant features of BrCa cells. Thus, identification of tumor‐suppressive miRNA and molecular networks controlled by these miRNA in BrCa cells may be an effective strategy for elucidation of the molecular pathogenesis of this disease.<br />We showed that miR‐101‐5p acted as an anti‐tumor miRNA in breast cancer (BrCa) cells through targeting several oncogenic genes (i.e. High Mobility Group Box 3, Epithelial splicing regulatory protein 1, GINS complex subunit 1 (GINS1), Tumor Protein D52, Serine/Arginine‐Rich Splicing Factor Kinase 1, Vang‐like protein 1, and Mago Homolog B). Aberrant expression of GINS1 mRNA and protein was observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126).
- Subjects :
- 0301 basic medicine
Cancer Research
endocrine system diseases
Carcinogenesis
0302 clinical medicine
Cell Movement
HMGB3 Protein
Genes, Tumor Suppressor
skin and connective tissue diseases
Research Articles
Aged, 80 and over
Gene knockdown
microRNA
pathogenesis
Cell Cycle
Nuclear Proteins
RNA-Binding Proteins
General Medicine
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
female genital diseases and pregnancy complications
Neoplasm Proteins
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Epithelial Splicing Regulatory Protein 1
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Female
Research Article
Adult
animal structures
tumor suppressor
Breast Neoplasms
Biology
lcsh:RC254-282
03 medical and health sciences
Splicing factor
breast cancer
miR‐101‐5p
Cell Line, Tumor
Genetics
Humans
Neoplasm Invasiveness
Gene Silencing
Gene
Aged
Cell Proliferation
Sequence Analysis, RNA
Membrane Proteins
MicroRNAs
030104 developmental biology
Tumor Protein D52
Cancer cell
Cancer research
GINS1
Ectopic expression
Carrier Proteins
Transcriptome
Subjects
Details
- ISSN :
- 18780261
- Volume :
- 14
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecular oncology
- Accession number :
- edsair.doi.dedup.....c25f9adcd52e4819a1a77b4e0cbcd2b6