Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

Angius, Andrea; Cossu-Rocca, Paolo; Arru, Caterina; Muroni, Maria Rosaria; Rallo, Vincenzo; Carru, Ciriaco; Uva, Paolo; Pira, Giovanna; Orrù, Sandra; Miglio, Maria Rosaria De

doi:10.3390/cancers12113298

Cited by 16 publications

(9 citation statements)

References 208 publications

(227 reference statements)

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“…miR-21 Oncogenic Antiapoptotic activity, tumor proliferation, and drug resistance; enhancing migration and invasion Target gene(s): HIF1A (HIF1α), TIMP3, TM1 [70]; PDCD4, PTEN [70,71]; TPM1, TGFBR2 [71] [60]…”

Section: Therapeutic Applications Of Rna-based Methods For Treatment Of Tnbc 21 Pre-clinical Progress Of Rna-based Therapiesmentioning

confidence: 99%

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RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

et al. 2021

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Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive cancer that has the highest mortality rate out of all breast cancer subtypes. Conventional clinical treatments targeting ER, PR, and HER2 receptors have been unsuccessful in the treatment of TNBC, which has led to various research efforts in developing new strategies to treat TNBC. Targeted molecular therapy of TNBC utilizes knowledge of key molecular signatures of TNBC that can be effectively modulated to produce a positive therapeutic response. Correspondingly, RNA-based therapeutics represent a novel tool in oncology with their ability to alter intrinsic cancer pathways that contribute to poor patient prognosis. Current RNA-based therapeutics exist as two major areas of investigation—RNA interference (RNAi) and RNA nanotherapy, where RNAi utilizes principles of gene silencing, and RNA nanotherapy utilizes RNA-derived nanoparticles to deliver chemotherapeutics to target cells. RNAi can be further classified as therapeutics utilizing either small interfering RNA (siRNA) or microRNA (miRNA). As the broader field of gene therapy has advanced significantly in recent years, so too have efforts in the development of effective RNA-based therapeutic strategies for treating aggressive cancers, including TNBC. This review will summarize key advances in targeted molecular therapy of TNBC, describing current trends in treatment using RNAi, combination therapies, and recent efforts in RNA immunotherapy, utilizing messenger RNA (mRNA) in the development of cancer vaccines.

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Section: Therapeutic Applications Of Rna-based Methods For Treatment Of Tnbc 21 Pre-clinical Progress Of Rna-based Therapiesmentioning

confidence: 99%

“…Select miRNA molecules and siRNA/shRNA molecular targets described in current preclinical studies on TNBC[60][61][62][63][64]71,.…”

mentioning

confidence: 99%

RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

et al. 2021

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“…For example, exosomes contain non-coding RNAs, especially miRNAs, which have been strongly suggested to be associated with the development of cancer [ 4 , 5 , 6 , 7 , 8 ]. MicroRNAs are small non-coding RNAs of approximately 20–25 nucleotides (nt) in length, with the ability to modulate gene expression by binding to specific regions at the 3′ UTR end of genes, inducing the repression or complete degradation of mRNAs [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Two Exosomal miRNAs in Circulating Blood of Cancer Patients by Using Integrative Transcriptome and Network Analysis

Rincón-Riveros

Rodríguez

Villegas

et al. 2022

ncRNA

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Exosomes carry molecules of great biological and clinical interest, such as miRNAs. The contents of exosomes vary between healthy controls and cancer patients. Therefore, miRNAs and other molecules transported in exosomes are considered a potential source of diagnostic and prognostic biomarkers in cancer. Many miRNAs have been detected in recent years. Consequently, a substantial amount of miRNA-related data comparing patients and healthy individuals is available, which contributes to a better understanding of the initiation, development, malignancy, and metastasis of cancer using non-invasive sampling procedures. However, a re-analysis of available ncRNA data is rare. This study used available data about miRNAs in exosomes comparing healthy individuals and cancer patients to identify possible global changes related to the presence of cancer. A robust transcriptomic analysis identified two common miRNAs (miR-495-3p and miR-543) deregulated in five cancer datasets. They had already been implicated in different cancers but not reported in exosomes circulating in blood. The study also examined their target genes and the implications of these genes for functional processes.

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“…TNBCs have been further subclassified into different groups based on definitions that might differ between studies [ 4 , 5 , 6 , 7 ]. Even if the classification of TNBCs is still subject of debate, a consensus would be a division into six subtypes displaying unique gene expression profiles, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem-like (MSL), and a luminal androgen receptor (LAR) subtype [ 5 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

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Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.

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Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

Cited by 16 publications

References 208 publications

RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

Identification of Two Exosomal miRNAs in Circulating Blood of Cancer Patients by Using Integrative Transcriptome and Network Analysis

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

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