scholarly journals MicroRNA Regulation of Breast Cancer Stemness

2021 ◽  
Vol 22 (7) ◽  
pp. 3756
Author(s):  
Brock Humphries ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Therapy Resistance ◽  
Outcome Data ◽  
Microrna Regulation ◽  
Cancer Initiation ◽  
Research Findings ◽  
Metastasis Therapy ◽  
Tumor Initiating Cell ◽  
Small Subpopulation

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.

scholarly journals MicroRNA Regulation of Epigenetic Modifiers in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 897 ◽  
Author(s):  
Brock Humphries ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Microrna Regulation ◽  
Epigenetic Biomarkers ◽  
Cancer Initiation ◽  
Research Findings ◽  
Aberrant Dna Methylation ◽  
Histone Modification Patterns

Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs themselves also indirectly drive these DNA and histone modifications. More explicitly, recent work has shown that miRNAs can regulate chromatin structure and gene expression by directly targeting key enzymes involved in these processes. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as epigenetic biomarkers and as therapeutics, and presents a comprehensive summary of currently validated epigenetic targets in breast cancer.

scholarly journals Novel Therapeutics Against Breast Cancer Stem Cells by Targeting Surface Markers and Signaling Pathways

2019 ◽  
Vol 14 (8) ◽  
pp. 669-682 ◽  
Author(s):  
Plabon K. Das ◽  
Md. A. Rakib ◽  
Jahan A. Khanam ◽  
Suja Pillai ◽  
Farhadul Islam
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Surface Markers ◽  
Breast Cancer Stem Cells ◽  
Novel Therapeutics ◽  
Cancer Pathogenesis

Background: Breast cancer remains to be one of the deadliest forms of cancers, owing to the drug resistance and tumor relapse caused by breast cancer stem cells (BCSCs) despite notable advancements in radio-chemotherapies. Objective: To find out novel therapeutics against breast cancer stem cells by aiming surface markers and signaling pathways. Methods: A systematic literature search was conducted through various electronic databases including, Pubmed, Scopus, Google scholar using the keywords "BCSCs, surface markers, signaling pathways and therapeutic options against breast cancer stem cell. Articles selected for the purpose of this review were reviewed and extensively analyzed. Results: Novel therapeutic strategies include targeting BCSCs surface markers and aberrantly activated signaling pathways or targeting their components, which play critical roles in self-renewal and defense, have been shown to be significantly effective against breast cancer. In this review, we represent a number of ways against BCSCs surface markers and hyper-activated signaling pathways to target this highly malicious entity of breast cancer more effectively in order to make a feasible and useful strategy for successful breast cancer treatment. In addition, we discuss some characteristics of BCSCs in disease progression and therapy resistance. Conclusion: BCSCs involved in cancer pathogenesis, therapy resistance and cancer recurrence. Thus, it is suggested that a multi-dimensional therapeutic approach by targeting surface markers and aberrantly activated signaling pathways of BCSCs alone or in combination with each other could really be worthwhile in the treatment of breast cancer.

scholarly journals A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2873
Author(s):  
Shu-Chun Chang ◽  
Chin-Sheng Hung ◽  
Bo-Xiang Zhang ◽  
Tsung-Han Hsieh ◽  
Wayne Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Mrna Level ◽  
Breast Carcinogenesis ◽  
E3 Ligases ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Cell Progression ◽  
F Box Protein ◽  
Cancer Activity

Breast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiquitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregulation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, suggesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpression reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.

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