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A Novel Bioengineered miR-127 Prodrug Suppresses the Growth and Metastatic Potential of Triple-Negative Breast Cancer Cells
- Source :
- Cancer research, vol 80, iss 3, Cancer Res
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- miR-127 is downregulated in breast cancer, where it has been shown to suppress the proliferation, migration, and invasion of breast cancer cells. In triple-negative breast cancer (TNBC), miR-127 downregulation correlates with decreased disease-free and overall patient survival. Tumor suppressor miRNAs may hold therapeutic promise but progress has been limited by several factors, including the lability and high cost of miRNA mimics. Here, we take a novel approach to produce a miR-127 prodrug (miR-127PD), which we demonstrate is processed to mature, functional miR-127-3p in TNBC tumor cells. miR-127PD decreased the viability and motility of TNBC cells, sensitized TNBC cells to chemotherapy, and restricted the TNBC stem cell population. Furthermore, systemic delivery of miR-127PD suppressed tumor growth of MDA-MB-231 and MDA-MB-468 TNBC cells and spontaneous metastasis of MDA-MB-231 cells. In addition, CERK, NANOS1, FOXO6, SOX11, SOX12, FASN, and SUSD2 were identified as novel, functionally important targets of miR-127. In conclusion, our study demonstrates that miR-127 functions as a tumor and metastasis suppressor in TNBC and that delivery of miR-127 may hold promise as a novel therapy. Significance: Exogenous administration of miR-127, which is functionally activated in target cells, inhibits growth and spontaneous metastasis of triple-negative breast cancer.
- Subjects :
- 0301 basic medicine
Cancer Research
Lung Neoplasms
medicine.medical_treatment
Apoptosis
Triple Negative Breast Neoplasms
Mice, SCID
law.invention
Mice
0302 clinical medicine
law
Mice, Inbred NOD
Tumor Cells, Cultured
Medicine
2.1 Biological and endogenous factors
Prodrugs
Aetiology
Triple-negative breast cancer
Cancer
Cultured
Tumor
Prodrug
Prognosis
Tumor Cells
Gene Expression Regulation, Neoplastic
Survival Rate
Oncology
030220 oncology & carcinogenesis
Lymphatic Metastasis
Female
Biotechnology
Oncology and Carcinogenesis
Antineoplastic Agents
SCID
Article
SOXC Transcription Factors
03 medical and health sciences
Breast cancer
Downregulation and upregulation
microRNA
Breast Cancer
Biomarkers, Tumor
Animals
Humans
Metastasis suppressor
Oncology & Carcinogenesis
Cell Proliferation
Chemotherapy
Neoplastic
business.industry
medicine.disease
Xenograft Model Antitumor Assays
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Cancer research
Suppressor
Inbred NOD
business
Biomarkers
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cancer research, vol 80, iss 3, Cancer Res
- Accession number :
- edsair.doi.dedup.....cd0b6c971f834afd6eb8be6625f9df20