scholarly journals Identification of the Novel Tumor Suppressor Role of FOCAD/miR-491-5p to Inhibit Cancer Stemness, Drug Resistance and Metastasis via Regulating RABIF/MMP Signaling in Triple Negative Breast Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2524
Author(s):  
Wei-Chieh Huang ◽  
Hsiang-Cheng Chi ◽  
Shiao-Lin Tung ◽  
Po-Ming Chen ◽  
Ya-Chi Shih ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Tumor Suppressor ◽  
Pulmonary Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
High Expression ◽  
The Novel ◽  
Cancer Stemness

Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p in TNBC has never been elucidated. In this study, we reported the novel tumor suppressor function of FOCAD/miR-491-5p in TNBC. High expression of miR-491-5p was found to be associated with better overall survival in breast cancer patients. We found that miR-491-5p could be an intronic microRNA processed form FOCAD gene. We are the first to demonstrate that both miR-491-5p and FOCAD function as tumor suppressors to inhibit cancer stemness, epithelial-mesenchymal transition, drug resistance, cell migration/invasion, and pulmonary metastasis etc. in TNBC. MiR-491-5p was first reported to directly target Rab interacting factor (RABIF) to downregulate RABIF-mediated TNBC cancer stemness, drug resistance, cell invasion, and pulmonary metastasis via matrix metalloproteinase (MMP) signaling. High expression of RABIF was found to be correlated with poor clinical outcomes of breast cancer and TNBC patients. Our data indicated that miR-491-5p and RABIF are potential prognostic biomarkers and targeting the novel FOCAD/miR-491-5p/RABIF/MMP signaling pathway could serve as a promising strategy in TNBC treatment.

scholarly journals Role of SMC1 in Overcoming Drug Resistance in Triple Negative Breast Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64338 ◽  
Author(s):  
Sushma Yadav ◽  
Archana Sehrawat ◽  
Zeynep Eroglu ◽  
George Somlo ◽  
Robert Hickey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

Identification of the Novel Role of CD24 as an Oncogenesis Regulator and Therapeutic Target for Triple-Negative Breast Cancer

2018 ◽  
Vol 18 (1) ◽  
pp. 147-161 ◽  
Author(s):  
Shih-Hsuan Chan ◽  
Kuo-Wang Tsai ◽  
Shu-Yi Chiu ◽  
Wen-Hung Kuo ◽  
Heng-Yi Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Triple Negative ◽  
The Novel

scholarly journals Tumor suppressor role of microRNA-1296 in triple-negative breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (15) ◽  
pp. 19519-19530 ◽  
Author(s):  
Binh Phan ◽  
Shahana Majid ◽  
Sarah Ursu ◽  
David de Semir ◽  
Mehdi Nosrati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

scholarly journals 19P A dichotomous oncogenic role of the splicing factor SF3A3 in MYC-driven triple-negative breast cancer

2021 ◽  
Vol 32 ◽  
pp. S28
Author(s):  
A. Bosch ◽  
M. Cieśla ◽  
P. Cao Thi Ngoc ◽  
S. Mutukumar ◽  
G. Honeth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Splicing Factor

scholarly journals Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 549
Author(s):  
Amal Qattan ◽  
Taher Al-Tweigeri ◽  
Wafa Alkhayal ◽  
Kausar Suleman ◽  
Asma Tulbah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Drug Response ◽  
Triple Negative ◽  
Meta Analysis ◽  
Integrated Analysis ◽  
Circulating Mirnas ◽  
Persistent Problem ◽  
Network Analyses

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC.

scholarly journals The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 462
Author(s):  
Víctor Mayoral-Varo ◽  
María Pilar Sánchez-Bailón ◽  
Annarica Calcabrini ◽  
Marta García-Hernández ◽  
Valerio Frezza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Sh2 Domain ◽  
Model Systems ◽  
System A ◽  
Promising Therapeutic Target ◽  
Relevant Role ◽  
Inactivating Mutation

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative.

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