The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors

Tormo, Eduardo; Ballester, Sandra; Adam‐Artigues, Anna; Burgués, Octavio; Alonso, Elisa; Bermejo, Begoña; Menéndez, Sílvia; Zazo, Sandra; Madoz‐Gúrpide, Juan; Rovira, Ana; Albanell, Joan; Rojo, Federico; Lluch, Ana; Eroles, Pîlar

doi:10.1038/s41598-019-41472-y

Cited by 70 publications

(46 citation statements)

References 40 publications

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“…miRNA-143-3p increase the sensitivity of TNBC to paclitaxel by inferenig with CIAPIN1 expression, a cytokineinduced apoptosis inhibitor 1 protein [161]. miR-449 can induce doxorubicin respone in TNBC by downregulating cell cycle related genes [162]. Such combinations, which are already tested in BC preclinical models have the potential to be tested for BCBM.…”

Section: Mirna and Bcbm Therapeuticsmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.Keywords: Breast cancer brain metastasis, miRNA, Brain tumor microenvironment, Blood-brain barrier, CNS metastasis

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Section: Mirna and Bcbm Therapeuticsmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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“…In China, incidence rate is growing at more than twice the rate of global growth, especially in urban areas [4]. Triple negative breast cancer (TNBC) is a subtype of breast cancer which lack of estrogen receptor, progesterone receptor and low expression of human epidermal growth factor receptor 2 (HER 2) [7][8][9]. Due to these, the prognosis was worse than other subtypes of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3

et al. 2019

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Background: Breast cancer is the second common malignant cancer among females worldwide. Accumulating studies have indicated that deregulation of miRNA expression in breast cancer will contribute to tumorigenesis and form different cancer subtypes. However, the reported studies on miR-29b-3p-regulated breast cancer are limited so far. Herein, we investigated the role and mechanism of miR-29b-3p in the triple negative breast cancer cell line MDA-MB-231. Methods: The relative miR-29b-3p expression in different breast cancer cell lines were determined by qRT-PCR. CCK8 and colony formation assay were used to determine the influence of miR-29b-3p on cell proliferation. Migration assay and invasion assay were performed for cell migration and invasion respectively. To study the cell integrity immunofluorescence was performed. TUNEL assay, flow cytometry assay, hoechst staining and western blot were conducted to determine the influence of miR-29b-3p inhibitor on cell apoptosis. TRAF3 was found to be the target gene of miR-29b-3p using bioinformatics predictions. Dual-luciferase assay was performed to determine the relative luciferase activity in NC, miR-29b-3p mimic, miR-29b-3p inhibitor with TRAF3 3′-UTR wt or TRAF3 3′-UTR mt reporter plasmids. The proteins expression of NF-κB signaling pathway in MDA-MB-231 after transfection with NC, miR-29b-3p mimic, miR-29b-3p inhibitor were determined by western blot. Results: The miR-29b-3p expression was significantly increased in MDA-MB-231 compare with MCF-10A. miR-29b-3p inhibitor reduced the cell viability of MDA-MB-231 and inhibited cell migration and invasion. Cell cytoskeleton integrity destroyed after miR-29b-3p inhibitor treatment. Furthermore, we identified the mechanism and found miR-29b-3p targets the TRAF3 and activates NF-κB signaling pathway. Conclusions: From the above studies, our results indicated that miR-29b-3p acts as a promoter for the development of MDA-MB-231.

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“…Tormo et al showed that miR-449 affects prognosis, mainly by regulating the response of TNBC to the chemotherapy drug doxorubicin. The high expression of miR-449a was significantly associated with a good prognosis by Metabric study-GEO database, while miR-449b/c was not associated with prognosis [186]. Tsiakou et al analyzed the single nucleotide polymorphisms (SNPs) of miR-34, and the result showed that the TNBC patients with TC/CC genotype in the rs4938723 C>T polymorphism had shorter OS intervals with worse prognosis [187].…”

Section: Prognostic Implications Of Mirnas In Tnbcmentioning

confidence: 99%

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer

Ding

Xiong

et al. 2019

Cells

118

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Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3′-untranslated region (3′-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial–mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.

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The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors

Cited by 70 publications

References 40 publications

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer

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