MicroRNA Regulation of Breast Cancer Stemness

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 30

PMID 33916548

Citations 11

Authors

Brock Humphries

Zhishan Wang

Chengfeng Yang

Affiliations

Soon will be listed here.

Abstract

Recent advances in our understanding of breast cancer have demonstrated that cancer stem-like cells (CSCs, also known as tumor-initiating cell (TICs)) are central for progression and recurrence. CSCs are a small subpopulation of cells present in breast tumors that contribute to growth, metastasis, therapy resistance, and recurrence, leading to poor clinical outcome. Data have shown that cancer cells can gain characteristics of CSCs, or stemness, through alterations in key signaling pathways. The dysregulation of miRNA expression and signaling have been well-documented in cancer, and recent studies have shown that miRNAs are associated with breast cancer initiation, progression, and recurrence through regulating CSC characteristics. More specifically, miRNAs directly target central signaling nodes within pathways that can drive the formation, maintenance, and even inhibition of the CSC population. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as biomarkers and promising clinical therapeutics, and presents a comprehensive summary of currently validated targets involved in CSC-specific signaling pathways in breast cancer.

Citing Articles

Non-Coding RNAs in Breast Cancer: Diagnostic and Therapeutic Implications.

Benacka R, Szaboova D, Gulasova Z, Hertelyova Z Int J Mol Sci. 2025; 26(1.

PMID: 39795985 PMC: 11719911. DOI: 10.3390/ijms26010127.

Extracellular Vesicle-Mediated Modulation of Stem-like Phenotype in Breast Cancer Cells under Fluid Shear Stress.

Brown S, Radcliffe M, Danner J, Andujar Cruz W, Lackey K, Park H Biomolecules. 2024; 14(7).

PMID: 39062471 PMC: 11274421. DOI: 10.3390/biom14070757.

Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.

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PMID: 38360641 PMC: 10870553. DOI: 10.1186/s12964-024-01510-3.

Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.

Zablon F, Desai P, Dellinger K, Aravamudhan S Adv Biol (Weinh). 2024; 8(4):e2300532.

PMID: 38258348 PMC: 11198028. DOI: 10.1002/adbi.202300532.

Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis.

Nogueras Perez R, Heredia-Nicolas N, de Lara-Pena L, Andres J, Marchal J, Jimenez G Int J Mol Sci. 2023; 24(21).

PMID: 37958993 PMC: 10647353. DOI: 10.3390/ijms242116010.

References

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

OShea J, Gadina M, Schreiber R . Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002; 109 Suppl:S121-31. DOI: 10.1016/s0092-8674(02)00701-8. View

Li Y, Xiao Y, Lin H, Reichel D, Bae Y, Lee E . In vivo β-catenin attenuation by the integrin α5-targeting nano-delivery strategy suppresses triple negative breast cancer stemness and metastasis. Biomaterials. 2018; 188:160-172. DOI: 10.1016/j.biomaterials.2018.10.019. View

Brooks M, Burness M, Wicha M . Therapeutic Implications of Cellular Heterogeneity and Plasticity in Breast Cancer. Cell Stem Cell. 2015; 17(3):260-71. PMC: 4560840. DOI: 10.1016/j.stem.2015.08.014. View

Karamboulas C, Ailles L . Developmental signaling pathways in cancer stem cells of solid tumors. Biochim Biophys Acta. 2012; 1830(2):2481-95. DOI: 10.1016/j.bbagen.2012.11.008. View

Bahena-Ocampo I, Espinosa M, Ceballos-Cancino G, Lizarraga F, Campos-Arroyo D, Schwarz A . miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. EMBO Rep. 2016; 17(5):648-58. PMC: 5341522. DOI: 10.15252/embr.201540678. View

Cuk K, Zucknick M, Heil J, Madhavan D, Schott S, Turchinovich A . Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer. 2012; 132(7):1602-12. DOI: 10.1002/ijc.27799. View

Jiang Q, He M, Ma M, Wu H, Yu Z, Guan S . MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1. Oncol Rep. 2015; 35(3):1425-32. DOI: 10.3892/or.2015.4502. View

Xiao Y, Humphries B, Yang C, Wang Z . MiR-205 Dysregulations in Breast Cancer: The Complexity and Opportunities. Noncoding RNA. 2019; 5(4). PMC: 6958506. DOI: 10.3390/ncrna5040053. View

10.

Pal R, Maitra N, Mellon J, Khan M . Defining prostate cancer risk before prostate biopsy. Urol Oncol. 2012; 31(8):1408-18. DOI: 10.1016/j.urolonc.2012.05.012. View

11.

Saito Y, Jones P . Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle. 2006; 5(19):2220-2. DOI: 10.4161/cc.5.19.3340. View

12.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

13.

Kozomara A, Birgaoanu M, Griffiths-Jones S . miRBase: from microRNA sequences to function. Nucleic Acids Res. 2018; 47(D1):D155-D162. PMC: 6323917. DOI: 10.1093/nar/gky1141. View

14.

Polytarchou C, Iliopoulos D, Struhl K . An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state. Proc Natl Acad Sci U S A. 2012; 109(36):14470-5. PMC: 3437881. DOI: 10.1073/pnas.1212811109. View

15.

Li D, Ilnytskyy Y, Kovalchuk A, Khachigian L, Bronson R, Wang B . Crucial role for early growth response-1 in the transcriptional regulation of miR-20b in breast cancer. Oncotarget. 2013; 4(9):1373-87. PMC: 3824527. DOI: 10.18632/oncotarget.1165. View

16.

Vassilopoulos A, Chisholm C, Lahusen T, Zheng H, Deng C . A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer. Oncogene. 2013; 33(47):5477-82. DOI: 10.1038/onc.2013.516. View

17.

Zhong S, Li W, Chen Z, Xu J, Zhao J . MiR-222 and miR-29a contribute to the drug-resistance of breast cancer cells. Gene. 2013; 531(1):8-14. DOI: 10.1016/j.gene.2013.08.062. View

18.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

19.

Jiang C, Li D, Shi Z, Wang L, Liu M, Ge X . Estrogen regulates miRNA expression: implication of estrogen receptor and miR-124/AKT2 in tumor growth and angiogenesis. Oncotarget. 2016; 7(24):36940-36955. PMC: 5095050. DOI: 10.18632/oncotarget.9230. View

20.

Yang L, Tang H, Kong Y, Xie X, Chen J, Song C . LGR5 Promotes Breast Cancer Progression and Maintains Stem-Like Cells Through Activation of Wnt/β-Catenin Signaling. Stem Cells. 2015; 33(10):2913-24. DOI: 10.1002/stem.2083. View