MicroRNA and Breast Cancer: Understanding Pathogenesis, Improving Management

Eastlack, Steven

doi:10.3390/ncrna1010017

Cited by 21 publications

(17 citation statements)

References 142 publications

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“…MiR-155 is a well-known oncogenic miRNA, which is upregulated in a wide variety of human cancers (10, 11), especially in more aggressive and therapy resistant tumors (12, 13). For example, we identified a signature of deregulated miRNAs in patients with CLL and 17p deletion, versus patients with normal genotype, having good prognosis (14).…”

Section: Introductionmentioning

confidence: 99%

Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers

Roosbroeck

Fanini

Setoyama

et al. 2017

Clinical Cancer Research

134

127

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Purpose The oncogenic microRNA miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms through which miR-155 increases therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia and acute lymphoblastic leukemia. Results We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that miR-155 and TP53, the most frequently deregulated tumor suppressor, are linked in a negative feedback mechanism, and demonstrate that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions Our findings support the existence of a miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, still the main cause of cancer-related deaths.

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Section: Introductionmentioning

confidence: 99%

Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers

Roosbroeck

Fanini

Setoyama

et al. 2017

Clinical Cancer Research

134

127

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“…25,26 In order to exert their effects, mature miRNAs require ribonucleoprotein complexes, such as RNA-induced silencing complexes, to be assembled. 27 The mature single-stranded miRNAs that interact with the Argonaute proteins (AGO1, AGO2, AGO3 and AGO4) in RNA-induced silencing complexes typically bind to the 3′-untranslated regions of their cytosolic mRNA targets. These miRNAs inhibit the translation or promote the deadenylation and degradation of mRNA transcripts.…”

Section: Introductionmentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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“…The ability of this RNA-based tool of introducing singlenucleotide changes can be adapted for numerous therapeutic purposes, including modification of primary microRNA sequences with the final purpose of impairing the ability of the 'seed' sequence to bind and inhibit complementary genes. MicroRNAs have evolved as important regulators of carcinogenesis [40][41][42], where numerous therapeutic attempts are made with exogenous mimic or inhibitor sequences for the attenuation of malignant hallmarks [43][44][45][46]. However, the delivery method and its specificity, sometimes the necessity of multiple administrations and potential immunogenicity and toxicity of the exogenous sequence are just several factors that are hampering the clinical implementation of microRNA therapeutics.…”

Section: Is Rna-based Genetic Engineering the Safer Option?mentioning

confidence: 99%

CRISPR-based RNA editing: diagnostic applications and therapeutic options

Gulei

Ráduly

Berindan‐Neagoe

et al. 2019

Expert Review of Molecular Diagnostics

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Gene therapy is currently in the front rows of biomedical research with an increased focus on direct nuclease-based editing. If until now the research was mainly concentrated on modifications at the DNA level, new adapted tolls are starting to gain momentum due to their ability to induce changes within the RNA sequence. The advantage consists in the half-life of the messenger RNA and implicit the non-permanent character of the editing strategy. Recently, the ability of nucleases like Cas12a and Cas13 to cleave DNA and RNA, respectively, was used for detection of low particle infectious agents with high sensitivitye.g. DETECTOR and SHERLOCK Systems. The present article briefly presents the latest advancements from the gene editing therapeutic area, as well as the new diagnostic tools with great likelihoods within the clinical environment.

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MicroRNA and Breast Cancer: Understanding Pathogenesis, Improving Management

Cited by 21 publications

References 142 publications

Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers

Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

CRISPR-based RNA editing: diagnostic applications and therapeutic options

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