ER Negative Breast Cancer and miRNA: There Is More to Decipher Than What the Pathologist Can See!

Chamandi, Ghada; El-Hajjar, Layal; El Kurdi, Abdallah; Le Bras, Morgane; Nasr, Rihab; Lehmann-Che, Jacqueline

doi:10.3390/biomedicines11082300

Cited by 3 publications

(1 citation statement)

References 264 publications

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“…Some of these pathways are relevant in altering the response of TNBC to therapy by increasing cell sensitivity or reducing resistance [69]. The notion of miRNAs as biomarkers of TNBC [70][71][72] is still in its infancy. The heterogeneity of the disease, the incomplete annotation of miRNAs, and the variable technologies used for the identification of miRNAs are clear obstacles.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Ahram,

Abu Alragheb,

Abushukair

et al. 2024

Cancers

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It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Ahram,

Abu Alragheb,

Abushukair

et al. 2024

Cancers

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Synthesis and evaluation of chitosan/miR-125b nanoparticles for targeting Raf-1 and BMPR1b genes in MCF-7 breast cancer cells

Norouzi,

Abousalehi,

Afshar

2024

Preprint

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play important roles in cancer development and progression. MiR-125b-5p is a miRNA that has been reported to have diverse and context-dependent effects on different cancer types and subtypes. In this study, we aimed to investigate the expression and function of miR-125b-5p in MCF-7 breast cancer cells and to explore the potential of using chitosan nanoparticles for miR-125b-5p delivery. We found that miR-125b-5p was downregulated in MCF-7 cells compared to normal mammary epithelial cells, and that its overexpression reduced the viability of MCF-7 cells by targeting Raf-1 and BMPR1b genes, which are involved in cell survival and proliferation. We also synthesized and characterized chitosan/miR-125b nanoparticles (CNPs) and evaluated their in vitro release profile and cellular uptake. We showed that CNPs enhanced the delivery and efficiency of miR-125b-5p, resulting in a more potent inhibition of Raf-1 and BMPR1b gene expression and a greater reduction of cell viability. Our results suggest that miR-125b-5p and CNPs have potential anti-tumor effects on human breast cancer cells by suppressing Raf-1 and BMPR1b gene expression. Our study provides a new insight into the role and mechanism of miR-125b-5p and its target genes in breast cancer, and demonstrates the feasibility and efficacy of using chitosan nanoparticles for miR-125b-5p delivery.

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Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells

Farhana,

Alsrhani,

Alghsham

et al. 2024

IJMS

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MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanoparticles (GNP) against IL-6 overexpression and the modulation of miRNA-26a-5p in breast cancer (BC) cells. GNP were synthesized using the trisodium citrate method and characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). To predict the binding of miR-26a-5p in the IL-6 mRNA’s 3′UTR, we utilized bioinformatics algorithms. Luciferase reporter clone assays and anti-miRNA-26a-5p transfection were employed to validate the binding of miR26a-5p in the IL-6 mRNA’s 3′UTR. The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082. The synthesized GNP were spherical with a mean size of 28.3 nm, exhibiting high stability, and were suitable for BC cell treatment. We found that miR-26a-5p directly regulated IL-6 overexpression in MCF-7 cells activated with PMA. Treatment of MCF-7 cells with GNP resulted in the inhibition of IL-6 overexpression and secretion through the increase of miR26a-5p. Furthermore, GNP deactivated NF-κBp65/NF-κBp50 transcription activity. The newly engineered GNP demonstrated safety and showed promise as a therapeutic approach for reducing IL-6 overexpression. The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways.

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ER Negative Breast Cancer and miRNA: There Is More to Decipher Than What the Pathologist Can See!

Cited by 3 publications

References 264 publications

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Synthesis and evaluation of chitosan/miR-125b nanoparticles for targeting Raf-1 and BMPR1b genes in MCF-7 breast cancer cells

Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells

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