scholarly journals Aberrant alternative splicing in breast cancer

2019 ◽  
Vol 11 (10) ◽  
pp. 920-929 ◽  
Author(s):  
Quan Yang ◽  
Jinyao Zhao ◽  
Wenjing Zhang ◽  
Dan Chen ◽  
Yang Wang
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Gene Expression Regulation ◽  
Cancer Therapeutics ◽  
Cancer Drug ◽  
Splicing Factors ◽  
Cancer Drug Resistance ◽  
The Relationship

Abstract Alternative splicing is critical for human gene expression regulation, which plays a determined role in expanding the diversity of functional proteins. Importantly, alternative splicing is a hallmark of cancer and a potential target for cancer therapeutics. Based on the statistical data, breast cancer is one of the top leading causes of cancer-related deaths in women worldwide. Strikingly, alternative splicing is closely associated with breast cancer development. Here, we seek to provide a general review of the relationship between alternative splicing and breast cancer. We introduce the process of alternative splicing and its regulatory role in cancers. In addition, we highlight the functions of aberrant alternative splicing and mutations of splicing factors in breast cancer progression. Moreover, we discuss the role of alternative splicing in cancer drug resistance and the potential of being targets for cancer therapeutics.

Quest of EMT and CSC

2019 ◽  
Author(s):  
Shihori Tanabe
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Therapeutics ◽  
Cancer Drug ◽  
Phenotypic Change ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
The Relationship

Epithelial-mesenchymal transition (EMT), an important phenotypic change from epithelial to mesenchymal like cells, has the increasing impact for cancer progression in terms of the involvement in cancer stem cell (CSC). The EMT-featured cells and CSCs are important factors for the acquisition of cancer drug resistance. The understanding of EMT program activation is important for targeting CSCs in cancer therapy. The relationship between EMT and CSC in cancer therapeutics is focused in the editorial.

scholarly journals Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance

2012 ◽  
Vol 83 (8) ◽  
pp. 1084-1103 ◽  
Author(s):  
Karthika Natarajan ◽  
Yi Xie ◽  
Maria R. Baer ◽  
Douglas D. Ross
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Cancer Drug ◽  
Cancer Resistance ◽  
Cancer Drug Resistance ◽  
Resistance Protein

scholarly journals Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jie Mei ◽  
Tiejun Wang ◽  
Shaojie Zhao ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Suppressive Effect ◽  
Normal Breast ◽  
Bioinformatics Analyses ◽  
Novel Target ◽  
The Relationship

Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa via multiple bioinformatics analysis. Next, a series of in vitro experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.

Emerging Multi-cancer Regulatory Role of ESRP1: Orchestration of Alternative Splicing to Control EMT

2020 ◽  
Vol 20 (9) ◽  
pp. 654-665
Author(s):  
Yellamandayya Vadlamudi ◽  
Debasish K. Dey ◽  
Sun C. Kang
Keyword(s):  
Cell Proliferation ◽  
Alternative Splicing ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Target Genes ◽  
Rna Binding ◽  
Regulatory Protein ◽  
Cancer Therapeutics ◽  
Scientific Data

RNA binding proteins (RBPs) associate with nascent and mature RNAs to perform biological functions such as alternative splicing and RNA stability. Having unique RNA recognition binding motifs, RBPs form complexes with RNA in a sequence- and structure-based manner. Aberrant expressions of several RBPs have been identified in tumorigenesis and cancer progression. These uncontrolled RBPs affect several mechanisms, including cell proliferation, tumor growth, invasion, metastasis and chemoresistance. Epithelial splicing regulatory protein 1 (ESRP1) is a member of the hnRNP family of proteins that play a crucial role in regulating numerous cellular processes, including alternative splicing and translation of multiple genes during organogenesis. Abnormal expression of ESRP1 alters the cell morphology, and leads to cell proliferation and tumor growth during cancer progression. ESRP1 mediated alternative splicing of target genes, including CD44, FGFR, PTBP1, LYN, ENAH, SPAG1 and ZMYND8, results in cancer progression. In addition, ESRP1 also regulates circularization and biogenesis of circular RNAs such as circUHRF1, circNOL10 and circANKS1B, whose expressions have been identified as key factors in various cancers. This multi-functional protein is also involved in imposing stability of target mRNAs such as cyclin A2, and thereby cell cycle regulation. The scope of this review is to examine recent scientific data, outcomes of the up- and down-regulated proteins, and the role of ESRP1 in various cancers. We conclude by summarizing ESRP1 dysregulation and its consequences on target genes in various human cancers. Collectively, the consequences of ESRP1 mediated splicing in cancer cells suggest the role of ESRP1 in cell proliferation and chemoresistance via apoptosis and autophagy modulation, which could, therefore, be potential targets for cancer therapeutics.

scholarly journals The Role of Chemokines in Breast Cancer Pathology and Its Possible Use as Therapeutic Targets

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
M. Isabel Palacios-Arreola ◽  
Karen E. Nava-Castro ◽  
Julieta I. Castro ◽  
Eduardo García-Zepeda ◽  
Julio C. Carrero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Cancer Progression ◽  
Chemokine Receptors ◽  
Cancer Therapeutics ◽  
Receptor System ◽  
Small Proteins ◽  
Cancer Pathology ◽  
Breast Cancer Pathology

Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system.

scholarly journals Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect

2017 ◽  
Vol 114 (43) ◽  
pp. 11440-11445 ◽  
Author(s):  
Smriti Singh ◽  
Sathiya Pandi Narayanan ◽  
Kajal Biswas ◽  
Amit Gupta ◽  
Neha Ahuja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
The Warburg Effect

Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to normal PKM1 isoform. This results in the reversal of the Warburg effect and the inhibition of breast cancer cell growth, which may serve as a useful approach to inhibit the growth of breast cancer cells. Importantly, our results show that in addition to PKM splicing, BORIS also regulates the alternative splicing of several genes in a DNA methylation-dependent manner. Our findings highlight the role of intragenic DNA methylation and DNA binding protein BORIS in cancer-specific splicing and its role in tumorigenesis.

scholarly journals Correlations Between the Characteristics of Alternative Splicing Events, Prognosis, and the Immune Microenvironment in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Youyuan Deng ◽  
Hongjun Zhao ◽  
Lifen Ye ◽  
Zhiya Hu ◽  
Kun Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Immune Cell ◽  
Gene Expression Regulation ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Systematic Analysis

ObjectiveAlternative splicing (AS) is the mechanism by which a few genes encode numerous proteins, and it redefines the concept of gene expression regulation. Recent studies showed that dysregulation of AS was an important cause of tumorigenesis and microenvironment formation. Therefore, we performed a systematic analysis to examine the role of AS in breast cancer (Breast Cancer, BrCa) progression.MethodsThe present study included 993 BrCa patients from The Cancer Genome Atlas (TCGA) database in the genome-wide analysis of AS events. We used differential and prognostic analyses and found differentially expressed alternative splicing (DEAS) events and independent prognostic factors related to patients’ overall survival (OS) and disease-free survival (DFS). We divided the patients into two groups based on these AS events and analyzed their clinical features, molecular subtyping and immune characteristics. We also constructed a splicing factor (SF) regulation network for key AS events and verified the existence of AS events in tissue samples using real-time quantitative PCR.ResultsA total of 678 AS events were identified as differentially expressed, of which 13 and 10 AS events were independent prognostic factors of patients’ OS and DFS, respectively. Unsupervised clustering analysis based on these prognostic factors indicated that the Cluster 1 group had a better prognosis and more immune cell infiltration. SFs were significantly related to the expression of AS events, and AA-RPS21 was significantly upregulated in tumors.ConclusionAlternative splicing expands the mechanism of breast cancer progression from a new perspective. Notably, alternative splicing may affect the patient’s prognosis by affecting the infiltration of immune cells. Our research provides important guidance for subsequent studies of AS in breast cancer.

scholarly journals Exosomes and breast cancer drug resistance

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Xingli Dong ◽  
Xupeng Bai ◽  
Jie Ni ◽  
Hao Zhang ◽  
Wei Duan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Drug ◽  
Therapeutic Drug ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
Survival Signaling ◽  
Daunting Challenge

AbstractDrug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

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