Combining miR-10b–Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer

Yoo, Byunghee; Kavishwar, Amol; Ross, Alana; Wang, Ping; Tabassum, Doris P.; Polyák, Kornélia; Barteneva, Natalia; Petkova, Victoria; Pantazopoulos, Pamela; Tena, Aseda; Moore, Anna; Medarova, Zdravka

doi:10.1158/0008-5472.can-15-0888

Cited by 63 publications

(96 citation statements)

References 23 publications

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“…Recently, DEmiRNAs identified in TNBC have been found to be associated with the aggressive phenotype 14,15 . More importantly, emerging evidences have shown miRNAs could be applied to clinic as diagnostic/ prognostic biomarkers and therapeutic strategies for breast cancer [16][17][18] . Overall, identification of novel biomarkers for TNBC is currently a high priority, and miR-NAs as potential biomarkers, require better understanding of their roles and mechanisms in TNBC.…”

Section: Introductionmentioning

confidence: 99%

Exploring specific prognostic biomarkers in triple-negative breast cancer

Bao

Chen

et al. 2019

Cell Death Dis

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Lacking of both prognostic biomarkers and therapeutic targets, triple-negative breast cancer (TNBC) underscores pivotal needs to uncover novel biomarkers and viable therapies. MicroRNAs have broad biological functions in cancers and may serve as ideal biomarkers. In this study, by data mining of the Cancer Genome Atlas database, we screened out 4 differentially-expressed microRNAs (DEmiRNAs) between TNBC and normal samples: miR-135b-5p, miR-9-3p, miR-135b-3p and miR-455-5p. They were specially correlated with the prognosis of TNBC but not non-TNBC. The weighted correlation network analysis (WGCNA) for potential target genes of 3 good prognosis-related DEmiRNAs (miR-135b-5p, miR-9-3p, miR-135b-3p) identified 4 hub genes with highly positive correlation with TNBC subtype: FOXC1, BCL11A, FAM171A1 and RGMA. The targeting relationships between miR-9-3p and FOXC1/FAM171A1, miR-135b-3p and RGMA were validated by dual-luciferase reporter assays. Importantly, the regulatory functions of 4 DEmiRNAs and 3 verified target genes on cell proliferation and migration were explored in TNBC cell lines. In conclusion, we shed lights on these 4 DEmiRNAs (miR-135b-5p, miR-9-3p, miR-135b-3p, miR-455-5p) and 3 hub genes (FOXC1, FAM171A1, RGMA) as specific prognostic biomarkers and promising therapeutic targets for TNBC.

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Section: Introductionmentioning

confidence: 99%

Exploring specific prognostic biomarkers in triple-negative breast cancer

Bao

Chen

et al. 2019

Cell Death Dis

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“…Furthermore, miRs can transcriptionally inhibit the expression of target genes by binding to the 3'-untranslated region (3'-UTR), acting as oncogenes or tumor inhibitors (10). A growing number of studies have indicated that abnormal expression of miRs is associated with human breast cancer (11)(12)(13)(14)(15)(16). Furthermore, mounting evidence indicates that miRs serve key functions in the development of TNBC (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Yao

2018

Exp Ther Med

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Abstract. MicroRNA (miR)-146a-5p functions as a tumor suppressor in various types of cancer. However, the role of miR-146a-5p in the development of triple-negative breast cancer (TNBC) is unclear. The present study aimed to investigate the role of miR-146a-5p in TNBC. The expression level of miR-146a-5p in TNBC tissues and cell lines was initially detected using reverse transcription-quantitative polymerase chain reaction. To predict the target gene of miR-146a-5p, TargetScan software was used and a dual luciferase assay was performed to verify the prediction. Furthermore, in order to explore the role of miR-146a-5p in TNBC, miR-146a-5p was overexpressed in TNBC cells using miR-146a-5p mimics. An MTT assay was performed to detect cell proliferation, and a Transwell assay was conducted to determine cell migration and invasion. Furthermore, western blotting was performed to measure associated protein expression. It was revealed that miR-146a-5p was downregulated in TNBC tissues and cell lines. SOX5 was indicated to be a target gene of miR-146a-5p and was upregulated in TNBC cells. Additionally, miR-146a-5p could inhibit TNBC cell proliferation, migration and invasion, repress the expression of mesenchymal markers (N-cadherin, vimentin and fibronectin) and increase epithelial marker (E-cadherin) expression. Furthermore, SOX5 overexpression eliminated the effects of miR-146a-5p mimics on TNBC cells. In conclusion, the data of the present study indicated that miR-146a-5p inhibits the proliferation and metastasis of TNBC cells by regulating SOX5.

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“…Conversely, silencing miR-10b expression suppresses cancer cell proliferation, migration, and invasion in vitro as well as tumor growth or metastasis in vivo (14, 18, 19, 22), suggesting that miR-10b is a potential target for anti-tumor or anti-metastatic therapy. Notably, combining nanoparticle-encapsulated miR-10b inhibitors with low-dose doxorubicin achieved complete durable regression of metastases in a xenograft model of breast cancer (23). Intriguingly, miR-10b is secreted by metastatic breast cancer cells via exosomes and, upon uptake, induces invasiveness of non-malignant mammary epithelial cells (24).…”

Section: Introductionmentioning

confidence: 99%

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

et al. 2016

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The invasive and metastatic properties of many human tumors have been associated with upregulation of the microRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here we report the generation of miR-10b-deficient mice in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial-mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer. Among the target genes of miR-10b, the tumor suppressor genes Tbx5 and Pten and the metastasis suppressor gene Hoxd10 are significantly upregulated by miR-10b deletion. Mechanistically, miR-10b promotes breast cancer cell proliferation, migration, and invasion through inhibition of the expression of the transcription factor TBX5, leading to repression of the tumor suppressor genes DYRK1A and PTEN. In clinical specimens of breast cancer, the expression of TBX5, HOXD10, and DYRK1A correlates with relapse-free survival and overall survival outcomes in patients. Our results establish miR-10b as an oncomiR that drives metastasis, termed a metastamiR, and define the set of critical tumor suppressor mechanisms it overcomes to drive breast cancer progression.

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Combining miR-10b–Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer

Cited by 63 publications

References 23 publications

Exploring specific prognostic biomarkers in triple-negative breast cancer

Exploring specific prognostic biomarkers in triple-negative breast cancer

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

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