scholarly journals Study and Preparation of Multifunctional Poly(L-Lysine)@Hyaluronic Acid Nanopolyplexes for the Effective Delivery of Tumor Suppressive MiR-34a into Triple-Negative Breast Cancer Cells

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5309
Author(s):  
Jamila Djafari ◽  
Javier Fernández-Lodeiro ◽  
Hugo M. Santos ◽  
Julia Lorenzo ◽  
Sergi Rodriguez-Calado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Viral Gene ◽  
Tnbc Cell Line ◽  
Effective Delivery ◽  
Potential Strategy ◽  
Microrna Delivery ◽  
Viral Gene Delivery

Non-viral gene delivery using exogenous microRNAs is a potential strategy for fighting cancers with poor prognosis and which lack specific therapies, such as triple-negative breast cancer (TNBC). Herein we report the synthesis of six nontoxic electrostatic polymeric nanocapsules (P1 to P6) for microRNA delivery in TNBC cells. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM) were used to characterize the nanopolyplexes, synthesized with Poly(L-Lysine) and hyaluronic acid (Ha). Studies on the activity of the ternary HA/PLI/miRNA-34 nanopolyplexes towards TNBC cell line MDA-MB-231 were conducted. The nanopolyplexes mediated intracellular restoration of tumor suppressor miR34a was evaluated by using Western blotting to quantify the expression level of the Bcl-2 protein. The results suggest that the P5, with a ratio PLI/Ha of 0.05, was the most promising for the delivery of miR-34a into TNBC cells; the P5 nanocapsules were able to reduce Bcl-2 expression at a protein level, and had an effect in the overall cell viability after 24 h treatment.

scholarly journals Integrated network analysis identifies hsa-miR-4756-3p as a regulator of FOXM1 in Triple Negative Breast Cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuanliang Gu ◽  
Wenjuan Wang ◽  
Xuyao Wang ◽  
Hongyi Xie ◽  
Xiaojuan Ye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Function ◽  
Integrated Network ◽  
Forkhead Box ◽  
Tnbc Cell Line ◽  
Signal Activation ◽  
Tgf Β1 ◽  
Integration Analysis

Abstract Both aberrantly expressed mRNAs and micro(mi)RNAs play important roles in cancer cell function, which makes integration analysis difficult. In this study, we first applied master regulator analysisalgorithm and confirmed hsa-miR-4756-3p as a candidate miRNA in triple negative breast cancer (TNBC) patients; hsa-miR-4756-3p could regulate TNBC cell line apoptosis, proliferation, migration, and cell cycle as well as suppress TGF-β1 signalling andtumour growth. In TNBC, forkhead box protein M1 (FOXM1)was found to be an hsa-miR-4756-3p target gene, and FOXM1 knockout completely inhibited hsa-miR-4756-3p-induced cell migration and metastasis, TGF-β1 signalling, and epithelial mesenchymal signal activation, which indicated that hsa-miR-4756-3p functions via the FOXM1-TGFβ1-EMT axis.

scholarly journals Preparation, Characterization, and Inhibition of Hyaluronic Acid Oligosaccharides in Triple-Negative Breast Cancer

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 436 ◽  
Author(s):  
Wenwei Han ◽  
Lili Song ◽  
Yingdi Wang ◽  
Youjing Lv ◽  
Xiangyan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Glucuronic Acid ◽  
Biological Function ◽  
Critical Component ◽  
Potential Value ◽  
And Migration

Hyaluronic acid (hyaluronan, HA) is a critical component of the extracellular matrix and plays an important biological function of interacting with different molecules and receptors. In this study, both odd- and even-numbered HA oligosaccharides (HAOs) with specific degrees of polymerization (DP) were prepared by different hydrochloric acid hydrolyses, and their structures were characterized by means of HPLC, ESI-MS, and NMR. The data show that the odd-numbered HAOs (DP3-11) have a glucuronic acid reducing end, while the even-numbered HAOs (DP2-10) have an N-acetylglucosamine reducing end. Biological evaluations indicated that all HAOs significantly inhibited the growth and migration of triple-negative breast cancer (TNBC) MDA-MB-231 cells. Among these oligosaccharides, the HA tetrasaccharide (DP4) was confirmed to be the minimum fragment necessary to inhibit MDA-MB-231 cells. Our data suggest that HAOs have potential value in the treatment of TNBC.

scholarly journals The oncogenic kinase NEK2 regulates an RBFOX2-dependent pro-mesenchymal splicing program in triple-negative breast cancer cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chiara Naro ◽  
Monica De Musso ◽  
Francesca Delle Monache ◽  
Valentina Panzeri ◽  
Pierre de la Grange ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Splice Variants ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Tnbc Cell ◽  
Tnbc Cell Line

Abstract Background Triple-negative breast cancer (TNBC) is the most heterogeneous and malignant subtype of breast cancer (BC). TNBC is defined by the absence of expression of estrogen, progesterone and HER2 receptors and lacks efficacious targeted therapies. NEK2 is an oncogenic kinase that is significantly upregulated in TNBC, thereby representing a promising therapeutic target. NEK2 localizes in the nucleus and promotes oncogenic splice variants in different cancer cells. Notably, alternative splicing (AS) dysregulation has recently emerged as a featuring trait of TNBC that contributes to its aggressive phenotype. Methods To investigate whether NEK2 modulates TNBC transcriptome we performed RNA-sequencing analyses in a representative TNBC cell line (MDA-MB-231) and results were validated in multiple TNBC cell lines. Bioinformatics and functional analyses were carried out to elucidate the mechanism of splicing regulation by NEK2. Data from The Cancer Genome Atlas were mined to evaluate the potential of NEK2-sensitive exons as markers to identify the TNBC subtype and to assess their prognostic value. Results Transcriptome analysis revealed a widespread impact of NEK2 on the transcriptome of TNBC cells, with 1830 AS events that are susceptible to its expression. NEK2 regulates the inclusion of cassette exons in splice variants that discriminate TNBC from other BC and that correlate with poor prognosis, suggesting that this kinase contributes to the TNBC-specific splicing program. NEK2 elicits its effects by modulating the expression of the splicing factor RBFOX2, a well-known regulator of epithelial to mesenchymal transition (EMT). Accordingly, NEK2 splicing-regulated genes are enriched in functional terms related to cell adhesion and contractile cytoskeleton and NEK2 depletion in mesenchymal TNBC cells induces phenotypic and molecular traits typical of epithelial cells. Remarkably, depletion of select NEK2-sensitive splice-variants that are prognostic in TNBC patients is sufficient to interfere with TNBC cell morphology and motility, suggesting that NEK2 orchestrates a pro-mesenchymal splicing program that modulates migratory and invasive properties of TNBC cells. Conclusions Our study uncovers an extensive splicing program modulated by NEK2 involving splice variants that confer an invasive phenotype to TNBCs and that might represent, together with NEK2 itself, valuable therapeutic targets for this disease.

Delivery of thymoquinone through hyaluronic acid-decorated mixed Pluronic® nanoparticles to attenuate angiogenesis and metastasis of triple-negative breast cancer

2020 ◽  
Vol 322 ◽  
pp. 357-374
Author(s):  
Saurav Bhattacharya ◽  
Avijit Ghosh ◽  
Santanu Maiti ◽  
Manisha Ahir ◽  
Gouranga H. Debnath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

scholarly journals Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells

2018 ◽  
Vol 66 ◽  
pp. 294-309 ◽  
Author(s):  
Manoj B. Parmar ◽  
Daniel Nisakar Meenakshi Sundaram ◽  
Remant Bahadur K.C. ◽  
Robert Maranchuk ◽  
Hamidreza Montazeri Aliabadi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Hyaluronic Acid ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Sirna Delivery ◽  
And Migration

scholarly journals Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediated mesenchymal phenotype

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Qing He ◽  
Hongyu Jing ◽  
Lucy Liaw ◽  
Lindsey Gower ◽  
Calvin Vary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Mesenchymal Phenotype ◽  
Matrigel Invasion ◽  
Tnbc Cell ◽  
Tnbc Cell Line ◽  
E Cadherin

Abstract Sprouty (Spry) proteins have been implicated in cancer progression, but their role in triple-negative breast cancer (TNBC), a subtype of lethal and aggressive breast cancer, is unknown. Here, we reported that Spry1 is significantly expressed in TNBC specimen and MDA-MB-231 cells. To understand Spry1 regulation of signaling events controlling breast cancer phenotype, we used lentiviral delivery of human Spry1 shRNAs to suppress Spry1 expression in MDA-MB-231, an established TNBC cell line. Spry1 knockdown MDA-MB-231 cells displayed an epithelial phenotype with increased membrane E-cadherin expression. Knockdown of Spry1 impaired MDA-MB-231 cell migration, Matrigel invasion, and anchorage-dependent and -independent growth. Tumor xenografts originating from Spry1 knockdown MDA-MB-231 cells grew slower, had increased E-cadherin expression, and yielded fewer lung metastases compared to control. Furthermore, suppressing Spry1 in MDA-MB-231 cells impaired the induction of Snail and Slug expression by EGF, and this effect was associated with increased EGFR degradation and decreased EGFR/Grb2/Shp2/Gab1 signaling complex formation. The same phenotype was also observed in the TNBC cell line MDA-MB-157. Together, our results show that unlike in some tumors, where Spry may mediate tumor suppression, Spry1 plays a selective role in at least a subset of TNBC to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype.

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