Exosomal miR-1246 is Involved in Tumorigenesis by Targeting THRB in Breast Cancer

Abstract Background: Exosomal miRNAs have drawn increasing attention as tumor biomarkers involving in tumorigenesis due to their stability. The aim of this study was to analyze the role of exosomal miR-1246 in breast cancer.Methods: The differentially expressed (DE) miRNAs in exosomes from the serum of breast cancer patients and healthy controls were investigated using RNA-seq. The potential pathogenic target genes and functional enrichment of these miRNAs were explored using bioinformatics. Additionally, the role of miR-1246 in migration, invasion and proliferation were investigated in breast cancer cells. The expression of THRB were detected by QRT-PCR. Kaplan-Meier plotter was used to perform survival analysis.Results: The results showed that the level of exosomal miR-1246 was significantly higher in breast cancer than in the control. MiR-1246 mimic treatment promoted invasion and migration in MDA-MB-231 cells by targeting THRB. Kaplan-Meier survival curves showed that patients with high miR-1246 expression exhibited poor OS compared with patients with low miR-1246 expression, especially those with metastatic breast cancer.Conclusion: Our study provides a better understanding of exosomal miR-1246 in the process of breast cancer. Exosomal miR-1246 could be a potential prognostic biomarker for breast carcinoma.

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The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

Nature Communications ◽

10.1038/s41467-021-24631-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Eui Jung Moon ◽

Stephano S. Mello ◽

Caiyun G. Li ◽

Jen-Tsan Chi ◽

Kaushik Thakkar ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Invasion ◽

Critical Role ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Invasion And Metastasis ◽

Stat3 Signaling ◽

Inducible Genes ◽

Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

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Co‑expression Network Analysis by WGCNA and Identify Potential Prognostic Markers Associated with Lung Metastasis in Breast Cancer

10.21203/rs.3.rs-182567/v1 ◽

2021 ◽

Author(s):

xixun zhang

Keyword(s):

Breast Cancer ◽

Network Analysis ◽

Lung Metastasis ◽

Prognostic Markers ◽

Clinical Information ◽

Preventive Treatment ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Breast Cancer Patients ◽

Kaplan Meier

Abstract Backgroud: Breast cancer (BC) is an aggressive cancer with a high percentage recurrence and metastasis. As one of the most common distant metastasis organ in breast cancer, lung metastasis has a worse prognosis than that of liver and bone. Therefore, it’s important to explore some potential prognostic markers associated with the lung metastasis in breast cancer for preventive treatment. Methods: In our study, transcriptomic data and clinical information of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules was built by Weighted gene co-expression network analysis (WGCNA) to find out the royalbule modules which is significantly associated with lung metastasis in breast cancer. Then, co-expression genes were analyzed for functional enrichment. Furthermore, the prognostic value of these genes was assessed by GEPIA Database and Kaplan-Meier Plotter. Results: Results showed that the hub genes, LMNB and CDC20, were up-regulated in breast cancer and indicated worse survival. Therefore, we speculate that these two genes play crucial roles in the process of lung metastasis in breast cancer, and can be used as potential prognostic markers in lung metastasis of breast cancer. Conclusion: Collectively, our study identified two potential key genes in the lung metastasis of breast cancer, which might be applied as the prognostic markers of the precise treatment in breast cancer with lung metastasis.

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Bridging the Gap: Investigating the Role of Social Workers in Supporting Metastatic Breast Cancer Patients in Nigeria

Social Work in Public Health ◽

10.1080/19371918.2021.1999878 ◽

2021 ◽

pp. 1-14

Author(s):

Agha Ali Agha ◽

Chinyere Onalu ◽

Runcie Chidebe

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Social Workers ◽

Cancer Patients ◽

Metastatic Breast ◽

Breast Cancer Patients

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Prognostic Value of CA 15.3 Kinetics for Metastatic Breast Cancer

The International Journal of Biological Markers ◽

10.1177/172460080201700403 ◽

2002 ◽

Vol 17 (4) ◽

pp. 231-238 ◽

Cited By ~ 14

Author(s):

B. De La Lande ◽

K. Hacene ◽

J.-L. Floiras ◽

N. Alatrakchi ◽

M.-F. Pichon

Keyword(s):

Breast Cancer ◽

Lead Time ◽

Prognostic Value ◽

Cox Model ◽

Metastatic Breast ◽

Control Group ◽

Breast Cancer Patients ◽

Ca 15.3 ◽

Kaplan Meier ◽

Kinetics Of

Up to 80% of breast cancer patients developing metastases have high levels of CA 15.3. We studied the prognostic implications of CA 15.3 kinetics in 119 patients before and at first metastasis by univariate and multivariate statistics. At first metastasis, CA 15.3 was elevated in 82.4% of patients, with a lead time (median 162 days) in 42.0% of them. Kaplan-Meier analysis showed overall survival (median 1477 days) to be significantly related to estrogen receptor (ER) and progesterone receptor (PgR) status (p=0.0001) and tumor size (p=0.025). The interval between diagnosis and first abnormal CA 15.3 (p=0.0001), the CA 15.3 concentration (p=0.013), and the presence or absence of a lead time (p=0.001) also had prognostic value. ER and PgR status (p=0.0005 and p=0.0103, respectively), metastasis-free interval (p=0.0003), existence of a CA 15.3 lead time (p=0.0028), and days from diagnosis to first abnormal CA 15.3 (p=0.0055) entered in the Cox model. After first metastasis (median survival 573 days), ER and PgR status (p=0.0001 and p=0.0004, respectively), existence of a lead time for CA 15.3 (p=0.0138), and the concentration of first abnormal CA 15.3 (p=0.0145) had individual prognostic value. In the Cox model ER status (p=0.0001), nodal status (p=0.0191), existence of a lead time for CA 15.3 (p=0.0033), days from diagnosis to first abnormal CA 15.3 (p=0.0132), and concentration of first abnormal CA 15.3 (p=0.0320) were found to be independent prognostic variables. Compared to a matched historical control group that was not monitored by CA 15.3 assaying (n=140), the study group had a significantly longer survival after the first metastasis (p=0.0005). In conclusion, the kinetics of CA 15.3 before the first metastasis is of prognostic value. When associated with 18-fluorodeoxyglucose imaging, serial CA 15.3 assays may help to implement early treatment of metastases.

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Abstract C17: Role of miR-135b in gemcitabine sensitivity for metastatic breast cancer patients

10.1158/1535-7163.targ-15-c17 ◽

2015 ◽

Author(s):

Anna Tessari ◽

Dario Palmieri ◽

Giovanni Nigita ◽

Dario Veneziano ◽

Sara Cresta ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Breast Cancer Patients

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TIPE1 suppresses the invasion and migration of breast cancer cells and inhibits epithelial-to-mesenchymal transition primarily via the ERK signaling pathway

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz099 ◽

2019 ◽

Vol 51 (10) ◽

pp. 1008-1015 ◽

Cited By ~ 3

Author(s):

Shusheng Qiu ◽

Wei Hu ◽

Qiuhong Ma ◽

Yi Zhao ◽

Liang Li ◽

...

Keyword(s):

Breast Cancer ◽

Western Blot ◽

Cancer Cells ◽

Blot Analysis ◽

Western Blot Analysis ◽

Breast Cancer Cells ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration

Abstract Tumor necrosis factor α-induced protein 8-like-1 (TIPE1) functions as an activator or a repressor in a tumor cell type-specific manner. However, the role of TIPE1 in breast cancer, especially regarding metastasis, is unknown. In this study, we aimed to investigate the TIPE1 expression in breast cancer tissues, the biological functions, and the underlying mechanisms of TIPE1 regarding the metastatic properties of breast cancer cells. The results of immunohistochemical staining and western blot analysis indicated that TIPE1 expression was associated with tumor size and lymph node metastasis, and the expression of TIPE1 was downregulated in the tissues of patients with lymph node metastasis. Transwell and wound healing assay results showed that TIPE1 inhibited the invasive and migratory capacities of breast cancer cells. Moreover, the epithelial-mesenchymal transition (EMT) was suppressed in TIPE1-overexpressing cells, as demonstrated by western blot analysis. In addition, western blot analysis also showed that TIPE1 reduced the expression levels of MMP2 and MMP9 and decreased the phosphorylation level of ERK. These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit EMT primarily via the ERK signaling pathway. Our findings revealed the anti-tumor metastasis role of TIPE1 in breast cancer and TIPE1 might be a new candidate prognostic indicator and a potential molecular target for the treatment of breast cancer.

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The role of circCNIH4 in the adipocyte's effects on metastasis of breast cancer cells.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13086 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13086-e13086

Author(s):

Xiu Chen ◽

Jinhai Tang

Keyword(s):

Breast Cancer ◽

Wound Healing ◽

Cell Invasion ◽

Invasion And Migration ◽

Non Invasive ◽

In Vivo Experiments ◽

And Migration ◽

Mcf 7

e13086 Background: Obesity is associated with the risk of breast cancer(BCa) incidence and development. However, biological changes in obesity BCa individuals are still uncertain. Nowadays, circCNIH4, one of novel non-coding RNAs, was found to be a non-invasive biomarker in cancers. Methods: We verified the cancer-promoting role of obesity in BCa patients by comparing BMI indexes of 33 BCa and 44 benign tumor patients. Then we cocultured viscera adipose cells(HPA-v) and BCa cells(MCF-7/H and MDA-MB-231/H) to confirm the function of adipocytes on metastasis of BCa cells through wound healing, transwell assays. In vivo experiments were also performed. We analyzed the expression level of circCNIH4 in MCF-7/H, MDA-MB-231/H and different subtypes of BCa cells by quantitative polymerase chain reaction. Simultaneously, we identified inhibited effects of circCNIH4 on metastasis of BCa cells by wound healing, transwell assays and verified the location of circCNIH4 by FISH. Luciferase Assay was used to detect harbored miRNA. Rescue experiments were then applied. Results: We found the BMI of BCa patients(24.37±2.51) was much higher than benign patients(22.97±2.91). Metastasis of BCa cells were obviously promoted after in vitro and in vivo experiments. Then we found the expression of circCNIH4 in MCF-7/H and MDA-MB-231/H were down-regulated 0.71 and 0.52 than that in MCF-7 and MDA-MB-231. Also, circCNIH4 was positively correlated with less aggressive types of BCa cells. Overexpression of circCNIH4 in MDA-MB-231 could suppress cell invasion and migration, while silencing of it in MCF-7 promoted cell invasion and migration. The FISH assay demonstrated that circCNIH4 mainly located in the cytoplasm and might function as a “sponge” for miRNA. MiR-135b functioned as a tumor promoter gene from data of 93 BCa patients (HR = 2.27; 1.01 − 5.12), and it could be captured by circCNIH4 via luciferase and rescued assays. Conclusions: In this study, we revealed that BMI or viscera adipocytes could deteriorate prognosis of BCa and circCNIH4 could be a novel biomarker for non-invasive BCa. In details, circCNIH4 mainly suppressed the adipocyte's pro-metastasis effects on BCa by capturing miR-135b.

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Analysis of miRNA signature differentially expressed in exosomes from adriamycin-resistant and parental human breast cancer cells

Bioscience Reports ◽

10.1042/bsr20181090 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 5

Author(s):

Wei-xian Chen ◽

Ling-yun Xu ◽

Qi Qian ◽

Xiao He ◽

Wen-ting Peng ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Genes ◽

Expression Profiles ◽

Functional Enrichment ◽

Differentially Expressed ◽

Systematic Evaluation ◽

Mirna Signature ◽

Exosomal Mirnas

A major cause of failure in chemotherapy is drug resistance of cancer cells. Exosomes have been introduced to spread chemoresistance through delivering miRNAs. However, a systematic evaluation of the exosomal miRNA expression profiles responsible for chemoresistance is still lacking. In the present study, miRNA signature differentially expressed in exosomes derived from adriamycin-resistant (A/exo) and parental breast cancer cells (S/exo) were analyzed by microarray and the results were confirmed by PCR. A total of 309 miRNAs were increased and 66 miRNAs were decreased significantly in A/exo compared with S/exo. Specifically, 52 novel miRNAs with increased expression levels >16.0-fold in A/exo were identified. After prediction of target genes for 13 of 52 selected novel miRNAs, pathway analysis, gene ontology (GO) terms, and protein–protein interactions (PPIs) were constructed. The results implied that these selected exosomal miRNAs inhibited target genes involved in transcriptional misregulation in cancer, MAPK, and Wnt signaling pathways. Functional enrichment analysis demonstrated that the target genes were mainly responsible for protein phosphorylation, transcription regulation, molecular binding, and kinase activity. In summary, the current bioinformatics study of exosomal miRNAs may offer a new understanding into mechanisms of chemoresistance, which is helpful to find potential exosomal miRNAs to overcome drug insensitivity in future breast cancer treatment.

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