MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells

Abstract Background Chemotherapy is one of the most common treatment options for breast cancer (BC) patients. However, about half of the BC patients are chemotherapeutic resistant. Doxorubicin (DOX) is considered as one of the first line drugs in the treatment of BC patients whose function is negatively affected by multi drug resistance. Due to the severe side effects of DOX, it is very important to diagnose the DOX resistant BC patients. Therefore, assessment of molecular mechanisms involved in DOX resistance can improve the clinical outcomes in BC patients by introducing the novel therapeutic and diagnostic molecular markers. MicroRNAs (miRNAs) as members of the non-coding RNAs family have pivotal roles in various cellular processes including cell proliferation and apoptosis. Therefore, aberrant miRNAs functions and expressions can be associated with tumor progression, metastasis, and drug resistance. Moreover, due to miRNAs stability in body fluids, they can be considered as non-invasive diagnostic markers for the DOX response in BC patients. Main body In the present review, we have summarized all of the miRNAs that have been reported to be associated with DOX resistance in BC for the first time in the world. Conclusions Since, DOX has severe side effects; it is required to distinguish the non DOX-responders from responders to improve the clinical outcomes of BC patients. This review highlights the miRNAs as pivotal regulators of DOX resistance in breast tumor cells. Moreover, the present review paves the way of introducing a non-invasive panel of prediction markers for DOX response among BC patients.

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Ectopic expression of PLC‐β2 in non‐invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR‐146a

Molecular Carcinogenesis ◽

10.1002/mc.22964 ◽

2019 ◽

Vol 58 (5) ◽

pp. 708-721 ◽

Cited By ~ 2

Author(s):

Valeria Bertagnolo ◽

Silvia Grassilli ◽

Stefano Volinia ◽

Yasamin Al‐Qassab ◽

Federica Brugnoli ◽

...

Keyword(s):

Tumor Cells ◽

Breast Tumor ◽

Ectopic Expression ◽

Protective Role ◽

Malignant Progression ◽

Breast Tumor Cells ◽

Non Invasive ◽

Invasive Breast Tumor

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A Non-Invasive Approach for Monitoring Breast Tumor Cells During Therapeutic Intervention

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/108497802753773829 ◽

2002 ◽

Vol 17 (2) ◽

pp. 205-212 ◽

Cited By ~ 5

Author(s):

Tandra R. Chaudhuri ◽

Zhihong Cao ◽

Cristina Rodríguez-Burford ◽

Albert F. LoBuglio ◽

Kurt R. Zinn

Keyword(s):

Tumor Cells ◽

Therapeutic Intervention ◽

Breast Tumor ◽

Invasive Approach ◽

Breast Tumor Cells ◽

Non Invasive

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Application of nanoparticles to reverse multi-drug resistance in cancer

Nanotechnology Reviews ◽

10.1515/ntrev-2016-0023 ◽

2016 ◽

Vol 5 (5) ◽

Cited By ~ 3

Author(s):

Jie Yang ◽

Haijun Zhang ◽

Baoan Chen

Keyword(s):

Drug Resistance ◽

Side Effects ◽

Conventional Method ◽

Therapeutic Agents ◽

Present Review ◽

Multi Drug Resistance ◽

Long Period

AbstractMulti-drug resistance (MDR) poses a large obstacle to various human malignancies. For a long period, combination of multiple therapeutic agents has been the conventional method used to reverse MDR in cancer. However, it is still not an effective method as rather than cancer its serious side effects causes patient’s death. Nanoparticles (NPs) are emerging as a class of therapeutics for cancer, including overcoming MDR. In the present review, we focus on the application of NPs to reverse MDR in cancer. Several kinds of NPs developed for the reversal of MDR are summarized. In addition, investigations

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HDAC6 Inhibitors Sensitize Claudin-high Breast Cancer Cells to Cysteine Depletion via Activation of PKCγ Signaling

10.21203/rs.3.rs-116022/v1 ◽

2020 ◽

Author(s):

Tahiyat Alothaim ◽

Morgan Charbonneau ◽

Xiaohu Tang

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cell Death ◽

Tumor Cells ◽

Breast Tumor ◽

Zinc Homeostasis ◽

Cancer Type ◽

Library Screening ◽

Compound Library ◽

Breast Tumor Cells

Abstract IntroductionTriple-negative breast cancer (TNBC) is a highly malignant breast cancer type with poor prognosis and lacks effective therapy. TNBC is not responsive to targeted therapy for hormone receptors and often exhibit resistance to current chemotherapeutic agents. Targeting tumor metabolism is an emergent strategy to treat cancer. Therefore, identification of tumor metabolic deregulations and development of effective targeted therapies are urgently needed.MethodsWe performed the epigenetic compound library screening in claudin-high breast tumor cells and identified therapeutical sensitizers to overcome the drug resistance of targeted cysteine-dependence therapy. Gene expression profiling were generated to analyze signaling pathways induced by the combined tubacin and cysteine deprivation treatment. Specific inhibitors, shRNA, and CRISPR/Cas9 gene editing approaches were used to target cellular proteins HDAC6 and PKCγ and examine their roles in cell death. Cell viability, RT-qPCR, and Western blotting assays were performed in cysteine-independent tumor cells to examine the anticancer effects of combined tubacin and cysteine deprivation treatment. ResultsWe found that TNBC has differential death responses to cysteine deprivation and the cysteine-dependence of TNBC corelates with the expression levels of claudin genes in addition to the classical EMT markers. To overcome drug resistance in claudin-high/cysteine-independent breast tumor cells, HDAC6 inhibitors were identified by the epigenetic compound library screening as potent sensitizers that synergize with cysteine deprivation to eradicate cysteine-independent tumor cells. Unexpectedly, HDAC6 knockout did not recapitulate the HDAC6 inhibitors-mediated synthetic lethality, indicating that HDAC6 is not the actual target of HDAC6 inhibitors in this context. Transcriptomic profiling revealed that HDAC6 inhibitors synergizes with cysteine depletion to trigger a profound gene transcriptional program. Notably, a zinc-related gene response was observed to accompany with a prominent increase of labile zinc in cells during cell death. We further showed that activation of PKCγ signaling is required to interfere cellular zinc homeostasis and drive HDAC6 inhibitors-mediated cell death.ConclusionOur study demonstrated that HDAC6 inhibitors function as potent sensitizers to overcome the resistance of cysteine deprivation in claudin-high breast tumor cells. Identification of such sensitizers would make the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.

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