scholarly journals High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer

2020 ◽  
Vol 21 (9) ◽  
pp. 3045 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Eriko Katsuta ◽  
Masanori Oshi ◽  
Judith C. Sporn ◽  
Li Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Taxonomy ◽  
The Cancer Genome Atlas ◽  
P53 Pathway ◽  
Mesenchymal Transition ◽  
Gene Sets ◽  
Aggressive Cancer

Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor suppressive microRNA which exerts its anti-cancer functions by playing a role in p53, apoptosis induction, and epithelial-mesenchymal transition (EMT) suppression. Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) cohorts were used to test our hypothesis that miR-34a high BCs translate to less aggressive cancer biology and better survival in large cohorts. There was no association between miR-34a expression levels and clinicopathological features of BC patients except for HER2 positivity. MiR-34a high expressing tumors were associated with lower Nottingham pathological grades and lower MKI67 expression. In agreement, high miR-34a tumors demonstrated lower GSVA scores of cell cycle and cell proliferation-related gene sets. High miR-34a tumors enriched the p53 pathway and apoptosis gene sets. Unexpectedly, high miR-34a tumors also associated with elevated EMT pathway score and ZEB1 and two expressions. MiR-34a expression did not associate with any distant metastasis. Further, high miR-34a tumors did not associate with better survival compared with miR-34a low tumors. In conclusion, the clinical relevance of miR-34a high expressing tumors was associated with suppressed cell proliferation, enhanced p53 pathway and apoptosis, but enhanced EMT and these findings did not reflect better survival outcomes in large BC patient cohorts.

scholarly journals Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

2020 ◽  
Vol 21 (16) ◽  
pp. 5744 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Li Yan ◽  
Jing Li Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cancer Biology ◽  
The Cancer Genome Atlas ◽  
Related Gene ◽  
Immune Microenvironment ◽  
Gene Sets ◽  
Tumor Immune Microenvironment ◽  
Er Positive

Cancer-associated adipocytes are known to cause inflammation, leading to cancer progression and metastasis. The clinicopathological and transcriptomic data from 2256 patients with breast cancer were obtained based on three cohorts: The Cancer Genome Atlas (TCGA), GSE25066, and a study by Yau et al. For the current study, we defined the adipocyte, which is calculated by utilizing a computational algorithm, xCell, as “intratumoral adipocyte”. These intratumoral adipocytes appropriately reflected mature adipocytes in a bulk tumor. The amount of intratumoral adipocytes demonstrated no relationship with survival. Intratumoral adipocyte-high tumors significantly enriched for metastasis and inflammation-related gene sets and are associated with a favorable tumor immune microenvironment, especially in the ER+/HER2- subtype. On the other hand, intratumoral adipocyte-low tumors significantly enriched for cell cycle and cell proliferation-related gene sets. Correspondingly, intratumoral adipocyte-low tumors are associated with advanced pathological grades and inversely correlated with MKI67 expression. In conclusion, a high amount of intratumoral adipocytes in breast cancer was associated with inflammation, metastatic pathways, cancer stemness, and favorable tumor immune microenvironment. However, a low amount of adipocytes was associated with a highly proliferative tumor in ER-positive breast cancer. This cancer biology may explain the reason why patient survival did not differ by the amount of adipocytes.

scholarly journals Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 653
Author(s):  
Masanori Oshi ◽  
Yoshihisa Tokumaru ◽  
Swagoto Mukhopadhyay ◽  
Li Yan ◽  
Ryusei Matsuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Biology ◽  
Drug Response ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Annexin A1 ◽  
Mesenchymal Transition ◽  
Gene Sets ◽  
Apoptosis Protein

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein overexpressed in pancreatic cancer (PC). ANXA1 expression has been shown to take part in a wide variety of cancer biology, including carcinogenesis, cell proliferation, invasion, apoptosis, and metastasis, in addition to the initially identified anti-inflammatory effect in experimental settings. We hypothesized that ANXA1 expression is associated with cell proliferation and survival in PC patients. To test this hypothesis, we analyzed 239 PC patients in The Cancer Genome Atlas (TCGA) and GSE57495 cohorts. ANXA1 expression correlated with epithelial–mesenchymal transition (EMT) but weakly with angiogenesis in PC patients. ANXA1-high PC was significantly associated with a high fraction of fibroblasts and keratinocytes in the tumor microenvironment. ANXA1 high PC enriched multiple malignant gene sets, including hypoxia, tumor necrosis factor (TNF)-α signaling via nuclear factor-kappa B (NF-kB), and MTORC1, as well as apoptosis, protein secretion, glycolysis, and the androgen response gene sets consistently in both cohorts. ANXA1 expression was associated with TP53 mutation alone but associated with all KRAS, p53, E2F, and transforming growth factor (TGF)-β signaling pathways and also associated with homologous recombination deficiency in the TCGA cohort. ANXA1 high PC was associated with a high infiltration of T-helper type 2 cells in the TME, with advanced histological grade and MKI67 expression, as well as with a worse prognosis regardless of the grade. ANXA1 expression correlated with a sensitivity to gemcitabine, doxorubicin, and 5-fluorouracil in PC cell lines. In conclusion, ANXA1 expression is associated with EMT, cell proliferation, survival, and the drug response in PC.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

scholarly journals MiR-205 Dysregulations in Breast Cancer: The Complexity and Opportunities

2019 ◽  
Vol 5 (4) ◽  
pp. 53 ◽  
Author(s):  
Xiao ◽  
Humphries ◽  
Yang ◽  
Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Therapy Resistance ◽  
Cancer Cell Proliferation ◽  
Mesenchymal Transition

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that downregulate target gene expression by imperfect base-pairing with the 3′ untranslated regions (3′UTRs) of target gene mRNAs. MiRNAs play important roles in regulating cancer cell proliferation, stemness maintenance, tumorigenesis, cancer metastasis, and cancer therapeutic resistance. While studies have shown that dysregulation of miRNA-205-5p (miR-205) expression is controversial in different types of human cancers, it is generally observed that miR-205-5p expression level is downregulated in breast cancer and that miR-205-5p exhibits a tumor suppressive function in breast cancer. This review focuses on the role of miR-205-5p dysregulation in different subtypes of breast cancer, with discussions on the effects of miR-205-5p on breast cancer cell proliferation, epithelial–mesenchymal transition (EMT), metastasis, stemness and therapy-resistance, as well as genetic and epigenetic mechanisms that regulate miR-205-5p expression in breast cancer. In addition, the potential diagnostic and therapeutic value of miR-205-5p in breast cancer is also discussed. A comprehensive list of validated miR-205-5p direct targets is presented. It is concluded that miR-205-5p is an important tumor suppressive miRNA capable of inhibiting the growth and metastasis of human breast cancer, especially triple negative breast cancer. MiR-205-5p might be both a potential diagnostic biomarker and a therapeutic target for metastatic breast cancer.

scholarly journals LncRNA DLX6-AS1 Contributes to Epithelial–Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis

2020 ◽  
Vol 29 ◽  
pp. 096368972092998 ◽  
Author(s):  
Chuang Du ◽  
Yan Wang ◽  
Yingying Zhang ◽  
Jianhua Zhang ◽  
Linfeng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

scholarly journals Hyperglycemia promotes Snail-induced epithelial–mesenchymal transition of gastric cancer via activating ENO1 expression

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Xu ◽  
Bang Chen ◽  
Shaopu Zhu ◽  
Jiawei Zhang ◽  
Xiaobo He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Gastrointestinal Malignancies ◽  
Mesenchymal Transition

Abstract Background Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear. Method Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion. Results Among the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC. Conclusions Our results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.

UBE2T knockdown inhibits cell growth and metastasis of breast cancer through Wnt/β-catenin pathway

2021 ◽  
Author(s):  
Tao Xueqin ◽  
Mei Jinhong ◽  
Huang Yuping
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Lines ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition

Abstract Background: Emerging evidences have demonstrated that Ubiquitin-conjugating enzyme E2T (UBE2T) is dysregulated and play critical roles in various cancers. With the development of sequencing technology, studies have discovered that UBE2T is overexpressed in breast cancer tissues. However, the biological roles of UBE2T in breast cancer are still far to clear. In the present study, Methods: We analyzed the UBE2T expression in the Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression of UBE2T in breast cancer cell lines. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by using CCK-8, EdU, Transwell and western blot assays.Results: UBE2T was highly expressed in breast cancer cell lines. Functional analysis revealed that silence or elevation of UBE2T inhibited or promoted the proliferation, migration, invasion and EMT and Wnt/β-catenin signaling pathway related markers of MCF-7 cells. Mechanically, blocking of Wnt/β-catenin pathway by XAV939 reversed the promotion effect of UBE2T overexpression on breast cancer cells’ proliferation, migration and invasion.Conclusion: Our findings emphasized that UBE2T may act as an oncogene via activating the Wnt/β-catenin pathway, which may provide a potential therapeutic target for the treatment of breast cancer.

scholarly journals High expression of JAM2 indicates better prognosis and immunotherapy response in breast cancer

2020 ◽  
Author(s):  
Yang Peng ◽  
Chi Qu ◽  
Yingzi Zhang ◽  
Beige Zong ◽  
Yong Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Molecular Taxonomy ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs

In our study, multiple databases were used to explore the potential role and underlying mechanism of junctional adhesion molecule B (JAM2) in breast cancer (BRCA). The data of JAM2 were downloaded from The Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Receiver operating characteristic (ROC) curve analysis was performed to analyze the area under the curve (AUC) of JAM2 expression correlated with normal breast tissue and breast cancer tissue. Gene set enrichment analysis (GSEA) was used to identify the potential biological mechanisms of the JAM2. The expression of JAM2 mRNA was downregulated in most tumors, including BRCA, which may be due to the hypermethylated status. The AUCs, which were 0.929 and 0.887 by the logistic regression and random forest algorithms, indicated that JAM2 mRNA expression has good diagnostic value in BRCA. Univariate and multivariate analyses indicated JAM2 as an independent prognostic factor for the overall survival of BRCA patients in both the TCGA cohort (HR = 0.62, P = 0.034) and METABRIC cohort (HR = 0.77, P = 0.001). GSEA showed that multiple tumor pathways were suppressed in the JAM2 high expression group. The expression of JAM2 was most positively related to the epithelial-mesenchymal transition (EMT) score (r = 0.38; P <0.01) by the reverse-phase protein array (RPPA) analysis. Patients with high JAM2 expression may be more sensitive to immunotherapy. 18 chemotherapy drugs that patients in the JAM2 low expression group were more sensitive to being identified. Our results demonstrated the diagnostic and prognostic value of JAM2. Analysis of the molecular mechanisms indicates the potential role of JAM2 as a tumor suppressor, and high JAM2 expression may predict a better immunotherapy response in BRCA.

scholarly journals LncRNA SNHG15 facilitates development of breast cancer (BC) by upregulating c-Myc through sponging miR-451

2020 ◽  
Author(s):  
Jiang Du ◽  
Hong Zhong ◽  
Binlin Ma
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Pearson Correlation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Blue Staining ◽  
Dependent Manner ◽  
Luciferase Reporter Gene ◽  
Mesenchymal Transition

Abstract Background: Emerging evidences suggested that LncRNA SNHG15 functioned as an oncogene to promote breast cancer (BC) progression, but the detailed mechanisms are still not fully delineated.Methods: The expression levels of the associated genes were examined by using the Real-Time qPCR and Western Blot. Dual-luciferase reporter gene system was performed to validated the potential targeting sites. Cell counting kit-8 and colony formation assay were used to measure cell proliferation, and trypan blue staining and Annexin V-FITC/PI double staining assay were performed to determine cell viability and apoptosis. Cell invasion and migration were examined by transwell and wound scratch assay, respectively. The tumor-bearing mice models were established, and immunohistochemistry (IHC) was conducted to examine expression and localization of Ki67 protein in tumor tissues.Results: Here we identified that LncRNA SNHG15 upregulated c-Myc to facilitate BC progression by sponging miR-451 in a competing endogenous RNA (ceRNA)-dependent manner in vitro and in vivo. Mechanistically, LncRNA SNHG15 and c-Myc were upregulated, while miR-451 was downregulated in BC cells and clinical tissues, compared to their normal counterparts. As expected, the Pearson correlation analysis results indicated that miR-451 negatively correlated with LncRNA SNHG15 and c-Myc, and LncRNA SNHG15 was positively relevant to c-Myc in BC tissues. Next, we validated that LncRNA SNHG15 sponged miR-451 to upregulate c-Myc in BC cells. Further gain- and loss-function experiments evidenced that LncRNA SNHG15 promoted, while miR-451 inhibited malignant phenotypes, including cell proliferation, viability, migration, invasion and epithelial-mesenchymal transition (EMT) in BC cells. Interestingly, the inhibiting effects of LncRNA SNHG15 ablation on BC progression were abrogated by both silencing miR-451 and overexpressing c-Myc.Conclusions: Collectively, the present study evidenced that targeting LncRNA SNHG15/miR-451/c-Myc signaling cascade was novel to hamper BC progression, and the potential underlying mechanisms were also uncovered, which broadened our knowledge in this field, and provided potential biomarkers for BC diagnosis and treatment.

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