Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and In Vitro Studies

2022 ◽  
Vol 22 ◽  
Author(s):  
Wei Shi ◽  
Lu Qi ◽  
Xiong-Bin You ◽  
Yu-Chi Chen ◽  
Yu-Lian Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Network Pharmacology ◽  
Cancer Tissue

Background: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. Methods: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. Results: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis-free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. Conclusion: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.

scholarly journals ”BIK/NBK Gene Expression as a Possible Marker of Circulating Breast Cancer Cells in Blood“

2011 ◽  
Vol 4 (1) ◽  
pp. 8-14
Author(s):  
E. Lopez-Munoz ◽  
N. Garcia-Hernandez ◽  
R. I. Penaloza-Espinosa ◽  
M. E. Gomez-Del Toro ◽  
G. Zarco-Espinosa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Mrna Gene

The detection of circulating breast cancer cells in blood could be of special interest as an indicator of diagnosis and prognosis, and for the selection of treatment. In a previous report, our research group determined gene expression profiles in samples of breast cancer tissue, identifying over-expression of the BIK/NBK mRNA gene in 90% of the analyzed samples. In this paper, we analyze the BIK/NBK gene expression as a possible biomarker of circulating breast cancer cells in blood. We demonstrate that the BIK/NBK gene expression is not a significant biomarker in the detection of circulating breast cancer cells in the blood of women with breast cancer. Several studies have evaluated the regulation of apoptosis by estrogens in breast cancer cells, demonstrating the importance of BIK/NBK protein, in estrogen-regulated breast cancer cell apoptosis, which suggests that the regulation of its expression may be an important therapeutic target or strategy in the management of cancer, and, although we did not find statistically significant differences among the patient groups to demonstrate that BIK/NBK gene expression is a biomarker of circulating breast cancer cells in blood, we consider it necessary to continue the study of this gene in breast cancer tissue and its role in the development and progression of breast cancer, its prognostic value, and its potential use as therapeutic target.

scholarly journals Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

2017 ◽  
Vol 95 (8) ◽  
pp. 873-886 ◽  
Author(s):  
Da-nian Dai ◽  
Yan Li ◽  
Bo Chen ◽  
Yong Du ◽  
Shi-bing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Cysteine Proteases ◽  
Migration And Invasion ◽  
List Type

Abstract Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer. Key messages High CST1 expression is negatively correlated with survival of breast cancer patients. CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells. CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer.

scholarly journals PNSA, a Novel C-Terminal Inhibitor of HSP90, Reverses Epithelial–Mesenchymal Transition and Suppresses Metastasis of Breast Cancer Cells In Vitro

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 117
Author(s):  
Aotong Zhang ◽  
Xin Qi ◽  
Fu Du ◽  
Guojian Zhang ◽  
Dehai Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation

Metastasis accounts for the vast majority of deaths in breast cancer, and novel and effective treatments to inhibit cancer metastasis remain urgently developed. The expression level of heat shock protein 90 (HSP90) in invasive breast cancer tissue is higher than in adjacent non-cancerous tissue. In the present study, we investigated the inhibitory effect of penisuloxazin A (PNSA), a novel C- terminal inhibitor of HSP90, on metastasis of breast cancer cells and related mechanism in vitro. We found that PNSA obviously affected adhesion, migration, and invasion of triple-negative breast cancer (TNBC) MDA-MB-231 cells and Trastuzumab-resistant JIMT-1 cells. Furthermore, PNSA was capable of reversing epithelial–mesenchymal transformation (EMT) of MDA-MB-231 cells with change of cell morphology. PNSA increases E-cadherin expression followed by decreasing amounts of N-cadherin, vimentin, and matrix metalloproteinases9 (MMP9) and proteolytic activity of matrix metalloproteinases2 (MMP2) and MMP9. Comparatively, the N-terminal inhibitor of HSP90 17-allyl-17-demethoxygeldanamycin (17-AAG) had no effect on EMT of MDA-MB-231 cells. PNSA was uncovered to reduce the stability of epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) proteins and thereby inhibiting their downstream signaling transductions by inhibition of HSP90. In addition, PNSA reduced the expression of programmed cell death-ligand 1 (PD-L1) to promote natural killer (NK) cells to kill breast cancer cells with a dose far less than that of cytotoxicity to NK cell itself, implying the potential of PNSA to enhance immune surveillance against metastasis in vivo. All these results indicate that PNSA is a promising anti-metastasis agent worthy of being studied in the future.

Cisplatin-resistant MDA-MB-231 Cell-derived Exosomes Increase the Resistance of Recipient Cells in an Exosomal miR-423-5p-dependent Manner

2019 ◽  
Vol 20 (10) ◽  
pp. 804-814 ◽  
Author(s):  
Bing Wang ◽  
Yuzhu Zhang ◽  
Meina Ye ◽  
Jingjing Wu ◽  
Lina Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Differential Expression ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cell Viability Assay ◽  
Transmission Electron

Background: Chemoresistance blunts the therapeutic effect of cisplatin (DDP) on Triple-Negative Breast Cancer (TNBC). Researchers have not determined to date whether exosomes confer DDP resistance to other breast cancer cells or whether exosomal transfer of miRNAs derived from DDP-resistant TNBC cells confer DDP resistance. Objective: The aim of this study was to investigate the role of exosomes in chemoresistance in breast cancer. Methods: MDA-MB-231 cells resistant to DDP (231/DDP) were established. Exosomes were isolated from 231/DDP cells (DDP/EXO) and characterized by measuring the levels of protein markers, nanoparticle tracking analysis and transmission electron microscopy. MDA-MB-231, MCF-7 and SKBR-3 cell lines were treated with the isolated DDP/EXOs and cell proliferation and cytotoxicity to DDP were evaluated using MTT assays and apoptosis analyses. Western blotting was used to examine P-glycoprotein (P-gp) expression. Additionally, a microarray was used to analyse microRNA (miRNA) expression profiles in MDA-MB-231 and 231/DDP exosomes. The effects on miRNAs were determined using RT-PCR. Exosomal miR-423-5p was extracted, and differential expression was verified. The MTT cell viability assay, flow cytometry, and Transwell and immunofluorescence assays were performed to determine if differential expression of miR-423-5p sensitized cells to DDP in vitro. Results: Under a transmission electron microscope, the isolated exosomes exhibited a round or oval shape with a diameter ranging between 40 and 100 nm. DDP/EXOs labelled with PKH67 were taken up by MDA-MB-231 cells. After an incubation with DDP/EXOs, the cell lines exhibited a higher IC50 value for cisplatin, P-gp expression, migration and invasion capabilities and a lower apoptosis rate. Furthermore, 60 miRNAs from exosomes derived from 231/DDP cells were significantly up-regulated compared to exosomes from MDA-MB-231 cells. Notably, compared to the corresponding sensitive exosomes, miR-370-3p, miR-423-5p and miR-373 were the most differentially expressed miRNAs in DDP-resistant exosomes. We chose miR-423-5p, and up-regulation and down-regulation of exosomal miR-423-5p expression significantly affected DDP resistance. Conclusions: Exosomes from DDP-resistant TNBC cells (231/DDP) altered the sensitivity of other breast cancer cells to DDP in an exosomal miR-423-5p dependent manner. Our research helps to elucidate the mechanism of DDP resistance in breast cancer.

Research on the Negatively Regulation of Long Intergenic Non-Coding RNA 00210 to miR-424-5p in Breast Cancer Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 520-526
Author(s):  
Xingguo Cui ◽  
Weiguang Xu
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Cell Behaviors ◽  
Non Coding Rna ◽  
Set Up ◽  
E Cadherin

In this work, we investigate the expression of long intergenic non-coding RNA 00210 (LINC00210) and its effects on the behavior of breast cancer cells. To this end, we measured LINC00210 and miR-424-5p expression using RT-qPCR. Bioinformatics, dual luciferase report experiments, and RT-qPCR were applied to determine the potential function of LINC00210 in the regulation of miR-424-5p. Four groups of T-47D cells were set up: si-NC, si-LINC00210, si-LINC00210 + anti-miR-NC, and si-LINC00210 + anti-miR-424-5p. Then, cell viability, apoptosis, migration, and invasion were detected, respectively. Western blot analysis was applied to measure the expression levels of E-cadherin, N-cadherin, Bax, and Bcl-2. Our results showed that breast cancer tissue highly expressed LINC00210 and slightly expressed miR-424-5p, and that a direct binding function of LINC00210 to miR-424-5p existed. Furthermore, many of the behaviors of T-47D cells in the si-LINC00210 group were affected, including reductions in cell viability, migration and invasion abilities, as well as decreased expressions of LINC00210, Ki67, Bcl-2, and N-cadherin, an increased apoptosis rate, and increased expressions of miR-424-5p, E-cadherin, and Bax. In addition, in comparison with the si-LINC00210 + anti-miR-NC group, the cell behaviors of T-47D cells in the si-LINC00210 + anti-miR-424-5p group were affected, including increased cell viability, migration and invasion abilities, and expressions of Ki67, Bcl-2, and N-cadherin, but reductions in E-cadherin and Bax. The results demonstrated the inhibitory effects of LINC00210 on T-47D cells, as well as the negative regulation of LINC00210 on miR-424-5p, leading to cell apoptosis. The results imply the potential value of LINC00210 as a therapeutic target for breast cancer.

scholarly journals CD44v6 Targeted by miR-193b-5p in the Coding Region Modulates the Migration and Invasion of Breast Cancer Cells

2020 ◽  
Vol 11 (1) ◽  
pp. 260-271 ◽  
Author(s):  
Song Hu ◽  
Manlin Cao ◽  
Yiqing He ◽  
Guoliang Zhang ◽  
Yiwen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Coding Region

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

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