Effect of Dual-Targeting MiR-4282 and ATP-Binding Cassette Sub-Family C Member 4 on Drug Resistance of Breast Cancer Cells and Its Molecular Mechanism

2020 ◽  
Vol 10 (4) ◽  
pp. 507-511
Author(s):  
Jie Zhao ◽  
Guoqin Jiang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Invasion And Migration ◽  
Dual Targeting ◽  
And Migration ◽  
Mcf 7

Background: The present study focused on the effects of dual-targeting MiR-4282 and ABCC4 on drug resistance of breast cancer cells and the molecular mechanisms, expecting to provide a new approach for treating drug-resistant breast cancer. Material and methods: MiR-4282 overexpression and ABCC4 interference double gene lentiviral vectors were constructed. CCK-8, flow cytometry, Transwell assay and scratch assay were used to determine the overexpression of A and B Group, as well as the expression, proliferation, apoptosis, invasion and migration of C and D Group cells respectively. CCK-8 assay was applied to detect doxorubicin sensitivity. WB was used to detect the expressions of ABCC4, p53 and P-gp proteins in each group. Results: Overexpression of MiR4282 and downregulation of ABCC4 expression inhibited proliferation, invasion and migration of the cells, impeded normal cell cycle progression, and promoted apoptosis of the cells. The effect of dual-targeting MiR-4282 and ABCC4 on cell function is more pronounced. The results of CCK-8 assay showed that overexpression of MiR-4282 and downregulation of ABCC4 expression significantly promoted the sensitivity of MCF-7-ADR to doxorubicin, and dual-targeting MiR-4282 and ABCC4 were sensitive to the cell. The promotion effect is more obvious. WB analysis showed that overexpression of MiR-4282 and downregulation of ABCC4 expression significantly inhibited p53 protein in the cells, plus the inhibitory effects of dual-targeting MiR-4282 and ABCC4 were more obvious. MiR-4282 overexpression could prominently inhibit P-gp protein expression in the cells. Conclusion: Overexpression of MiR-4282 and downregulation of ABCC4 expression inhibit the proliferation, invasion and migration of MCF-7-ADR.

scholarly journals Knockdown of lncRNA FOXD2-AS1 Inhibits Proliferation, Migration, and Drug Resistance of Breast Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qiaohong Nong ◽  
Shaokang Yu ◽  
Hui Hu ◽  
Xue Hu
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Invasion And Migration ◽  
And Migration ◽  
Mcf 7

Objective. In order to investigate the effect of lncRNA FOXD2-AS1 on breast cancer cells proliferation, migration, and drug resistance as well as its molecular mechanism. Methods. Real-time PCR was used to detect the expression of breast cancer tissues and cells from patients admitted to our hospital and the expression of lncRNA FOXD2-AS1 in MCF-7/ADR in adriamycin- (ADR-) resistant breast cancer cells. After interfering with or overexpressing lncRNA FOXD2-AS1 in MCF-7/ADR cells, cell proliferation, apoptosis, invasion, and migration were detected using CCK-8, flow cytometry, Transwell assay, and scratch test, respectively. The protein levels of PI3K, p-PI3K, AKT, and p-AKT in the PI3K/AKT signaling pathway were detected by Western blot. Results. lncRNA FOXD2-AS1 was upregulated in breast cancer tissues and cells and increased cell drug resistance to ADR. Downregulation of lncRNA FOXD2-AS1 inhibited invasion and migration of MCF-7/ADR cells, promoted apoptosis, increased chemosensitivity of MCF-7/ADR cells, and inhibited the activity of PI3K/AKT signaling pathway in MCF-7/ADR cells. Conclusions. lncRNA FOXD2-AS1 can promote the proliferation, invasion, migration, and drug resistance of breast cancer cells, inhibit apoptosis, and accelerate the development of breast cancer by positively regulating the PI3K/AKT signaling pathway.

scholarly journals Silencing of Sphingosine 1-Phosphate Receptors and Potassium Channels May Inhibits the Invasion and Migration of Breast Cancer

2021 ◽  
Author(s):  
Didem Turgut Cosan ◽  
Ahu SOYOCAK ◽  
İbrahim Uğur ÇALIŞ
Keyword(s):  
Breast Cancer ◽  
Potassium Channels ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Mcf 7

Abstract Molecular receptor signaling mechanisms play an important role in many pathophysiological processes, including breast cancer. The spread of cancer from peripheral tissue to distant organs by metastasis is the cause of death of most breast cancer patients. For that reason, the most important step in the treatment of cancer is to prevent metastasis. Sphingosine-1-phosphate receptors and potassium channels play role of cancer cell migration, invasion and they may interact with each other in the progression of cancer. In this study, it was aimed to determine the effects of combined silencing of receptors and channels on the invasion and migration of MCF-7 and MDA-MB-231 breast cancer cells and their interactions on cells. We examined the expression levels of S1P1, S1P3, Kv1.3, and Kv10.1 in MCF-7 and MDA-MB-231 breast cancer cell lines by qRT-PCR. The effects of migration and invasion of breast cancer cells were determined through invasian and wound healing assays. It was observed that high invasion and lateral motility in cells decreased with the combined silencing of S1P1, S1P3, Kv1.3 and Kv10.1 in both cell types. It has been determined that silencing the receptors and channels together is more effective than silencing individually. Our data demonstrated the roles of S1P receptors and potassium channels were associated with invasion and migration signaling pathway. Therefore, these are might be possible therapeutic target for breast cancer metastasis.

scholarly journals Downregulation of matriptase suppresses the PAR‑2/PLCγ2/PKC‑mediated invasion and migration abilities of MCF‑7 breast cancer cells

2021 ◽  
Vol 46 (6) ◽  
Author(s):  
Jeong-Mi Kim ◽  
Jinny Park ◽  
Eun-Mi Noh ◽  
Hyun-Kyung Song ◽  
Sang Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Mcf 7

scholarly journals ARTEMISININ MODULATING EFFECT ON HUMAN BREAST CANCER CELL LINES WITH DIFFERENT SENSITIVITY TO CYTOSTATICS

2017 ◽  
Vol 39 (1) ◽  
pp. 25-29 ◽  
Author(s):  
V F Chekhun ◽  
N Yu Lukianova ◽  
T Borikun ◽  
T Zadvornyi ◽  
A Mokhir
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Iron Homeostasis ◽  
Chemotherapeutic Agents ◽  
Fold Change ◽  
Breast Cancer Cell Lines ◽  
Cellular Iron ◽  
Mcf 7

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

scholarly journals MiR-142-5p Acts as a Significant Regulator Through Promoting Proliferation, Invasion, and Migration in Breast Cancer Modulated by Targeting SORBS1

2019 ◽  
Vol 18 ◽  
pp. 153303381989226 ◽  
Author(s):  
Weixuan Yu ◽  
Dongwei Li ◽  
Yunda Zhang ◽  
Cheukfai Li ◽  
Chuanzhao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Patterns ◽  
Sh3 Domain ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration ◽  
Low Expression

Background: Numerous researches have demonstrated that miR-142-5p plays significant roles in several cancers, although the functional characteristic of miR-142-5p in breast cancer has not been determined. This study is designed to explore the biological significance of miR-142-5p in breast cancer clinical implication and mechanism of action. Methods: The differential expression patterns of miR-142-5p and Sorbin and SH3 domain-containing protein 1 and correlations between them and clinical significances were analyzed based on data from database. The expression levels of miR-142-5p in breast cancer cells were detected using quantitative real-time polymerase chain reaction. Cell counting kit-8, transwell, and wound healing assays were used to explore the potential functions of miR-142-5p in breast cancer cells. In addition, bioinformatics prediction analysis and luciferase reporter assay were utilized to predict and identify the potential target gene of miR-142-5p. A rescue experiment was conducted by transfecting miR-142-5p inhibitors and si-Sorbin and SH3 domain-containing protein 1 into cells to explore miR-142-5p/Sorbin and SH3 domain-containing protein 1 pairs on breast cancer cells behaviors. Results: The analysis results showed that miR-142-5p was highly expressed in patients with breast cancer, while Sorbin and SH3 domain-containing protein 1 presented a trend of low expression. The clinical significances analysis suggested that the overexpression of miR-142-5p is closely correlated with metastasis, while low expression of Sorbin and SH3 domain-containing protein 1 is correlated with clinicopathological characteristics and poor overall survival in patients with breast cancer. In vitro exploration, the expression of miR-142-5p was upregulated in breast cancer cells and inhibition of miR-142-5p expression significantly reduced the proliferation, invasion, and migration of breast cancer cells. Through rescue experiments, breast cancer cells proliferation, invasion, and migration reduction induced by silencing of miR-142-5p were reversed via knockdown Sorbin and SH3 domain-containing protein 1. Conclusion: Our findings insinuate that miR-142-5p functions as a positive regulator of promoting breast cancer cells biological behaviors and clinical metastasis, possibly regulated by targeting Sorbin and SH3 domain-containing protein 1, thus providing valuable information in the development of preventive or even therapeutic strategies for utilizing miR-142-5p as a promising target.

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