scholarly journals Detection and analysis of long noncoding RNA expression profiles related to epithelial–mesenchymal transition in keloids

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhixiong Chen ◽  
Xi Chu ◽  
Jinghong Xu
Keyword(s):  
Differential Expression ◽  
Noncoding Rna ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Normal Skin ◽  
Differentially Expressed ◽  
Extracellular Matrix Protein ◽  
Mesenchymal Transition ◽  
Promote Cell Proliferation

Abstract Background The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of keloids is currently raising increasing attention. Long noncoding RNAs (lncRNAs) govern a variety of biological processes, such as EMT, and their dysregulation is involved in many diseases including keloid disease. The aim of this study was to identify differentially expressed EMT-related lncRNAs in keloid tissues versus normal tissues and to interpret their functions. Results Eleven lncRNAs and 16 mRNAs associated with EMT were identified to have differential expression between keloid and normal skin tissues (fold change > 1.5, P < 0.05). Gene Ontology (GO) analysis showed that these differentially expressed mRNAs functioned in the extracellular matrix, protein binding, the positive regulation of cellular processes, the Set1C/COMPASS complex and histone acetyltransferase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these mRNAs are involved in pathways in cancer. The lncRNA, XLOC_000587 may promote cell proliferation and migration by enhancing the expression of ENAH, while AF268386 may facilitate the invasive growth of keloids by upregulating DDR2. Conclusions We characterized the differential expression profiles of EMT-related lncRNAs and mRNAs in keloids, which may contribute to preventing the occurrence and development of keloids by targeting the corresponding signaling pathways. These lncRNAs and mRNAs may provide biomarkers for keloid diagnosis and serve as potential targets for the treatment of this disease.

scholarly journals Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Zhangxiang Zhao ◽  
YingYing Guo ◽  
Yaoyao Liu ◽  
Lichun Sun ◽  
Bo Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Breast Cancer Subtype ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Response Analysis ◽  
Mesenchymal Transition

AbstractLong non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness of LncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNA PTOV1-AS1 was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation of PTOV1-AS1 could downregulate TJP1 (ZO-1) and E-Cadherin, and upregulate Vimentin, which suggests PTOV1-AS1 may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.

scholarly journals Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2

2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Yan Chen ◽  
Lin Chen ◽  
Duanyang Hong ◽  
Zongyue Chen ◽  
Jingyu Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cellular Response ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
T Antigen ◽  
Extracellular Matrix Protein ◽  
Mesenchymal Transition ◽  
Calpain 2 ◽  
E Cadherin

AbstractThe extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial–mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix–cancer cell interactions.

scholarly journals EDIL3 promotes epithelial–mesenchymal transition and paclitaxel resistance through its interaction with integrin αVβ3 in cancer cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
J. Gasca ◽  
M. L. Flores ◽  
R. Jiménez-Guerrero ◽  
M. E. Sáez ◽  
I. Barragán ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Integrin Αvβ3 ◽  
Extracellular Matrix Protein ◽  
Paclitaxel Resistance ◽  
Mesenchymal Transition ◽  
Breast And Prostate Cancer

Abstract Epithelial–mesenchymal transition (EMT) has recently been associated with tumor progression, metastasis, and chemotherapy resistance in several tumor types. We performed a differential gene expression analysis comparing paclitaxel-resistant vs. paclitaxel-sensitive breast cancer cells that showed the upregulation of EDIL3 (EGF Like Repeats and Discoidin I Like Domains Protein 3). This gene codifies an extracellular matrix protein that has been identified as a novel regulator of EMT, so we studied its role in tumor progression and paclitaxel response. Our results demonstrated that EDIL3 expression levels were increased in paclitaxel-resistant breast and prostate cancer cells, and in subsets of high-grade breast and prostate tumors. Moreover, we observed that EDIL3 modulated the expression of EMT markers and this was impaired by cilengitide, which blocks the EDIL3–integrin αVβ3 interaction. EDIL3 knockdown reverted EMT and sensitized cells to paclitaxel. In contrast, EDIL3 overexpression or the culture of cells in the presence of EDIL3-enriched medium induced EMT and paclitaxel resistance. Adding cilengitide resensitized these cells to paclitaxel treatment. In summary, EDIL3 may contribute to EMT and paclitaxel resistance through autocrine or paracrine signaling in cancer cells. Blockade of EDIL3–integrin αVβ3 interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

Characterization of differential genetic expression profiles in mesenchymal and epithelial components of uterine and ovarian carcinosarcomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17104-e17104
Author(s):  
Abraham Hernandez Blanquisett ◽  
Raquel Lopez-Reig ◽  
Ignacio Romero ◽  
Jose Antonio Lopez-Guerrero ◽  
Isidro Machado ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
P Value ◽  
Stage At Diagnosis ◽  
Mesenchymal Transition ◽  
Array Normalization ◽  
History Of ◽  
Ovarian Carcinosarcoma ◽  
Predictive Role

e17104 Background: Gynecologic carcinosarcomas (GCS) are rare tumors with poor prognosis. Reasons include a high percentage of advanced stage at diagnosis and a low response to conventional treatments. GCS constitutes a model for research in both tumoral heterogeneity and the epithelial-mesenchymal transition (EMT) process. Our aim is to define molecular expression heterogeneity in GCS distinct morphologic components. Methods: A retrospective, single institution, IRB approved study of 13 patients diagnosed with GCS was undertaken. Total RNA was extracted from representative FFPE tissue blocks of both the epithelial and mesenchymal components. The expression profile for each component (n = 26) was determined using the GeneChip WT Pico Reagent Kit and the Clariom D Array (Affymetrix Inc., Santa Clara, CA, USA). Robust multi-array normalization (RMA) and t-statistics was used for detecting differentially expressed genes between the studied conditions. Genes with a p-value < 0.05 and with an absolute fold change (FC) value > 1.5 were selected as significant. Results: A total of 13 cases representing 26 distinct samples, 9 uterine (UCS) and 4 ovarian carcinosarcoma with a median age of 68 (range: 45-81), 38% presented FIGO IIIC-IV stage at diagnosis. Among UCS, 5 women had a previous personal history of breast cancer. A total of 101 genes appeared as differentially expressed between epithelial and mesenchymal components, highlighting 5 of them: HMGA2 (FC = 2.15, p = 0.04) and ERBB4 (FC = 2.14, p = 0.005) overexpressed in epithelial component and ANX2 (FC = 1.95, p = 0.0006), SPP1 (FC = 2.15, p = 0,005) and ERRFI1 (FC = 1.95, p = 0.001) overexpressed in mesenchymal component. Conclusions: This is the first expression profiling in GCS that helps identify candidate genes that show a distinct expression in mesenchymal and epithelial components that could have a potential prognostic and predictive role.

scholarly journals FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness

2017 ◽  
Vol 114 (29) ◽  
pp. 7683-7688 ◽  
Author(s):  
Tong Liu ◽  
Hao Zhang ◽  
Li Sun ◽  
Danyu Zhao ◽  
Peng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
Gene Signature ◽  
Extracellular Matrix Protein ◽  
Breast Cancers ◽  
Fibrous Sheath ◽  
Mesenchymal Transition

Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesis-related testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-inducedFSIP1knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial–mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1intonu/numice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed on Western blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial–mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy.

scholarly journals Tissue remodeling in eosinophilic esophagitis

2012 ◽  
Vol 303 (11) ◽  
pp. G1175-G1187 ◽  
Author(s):  
Edaire Cheng ◽  
Rhonda F. Souza ◽  
Stuart J. Spechler
Keyword(s):  
Mast Cells ◽  
Eosinophilic Esophagitis ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tissue Remodeling ◽  
Inflammatory Cells ◽  
Extracellular Matrix Protein ◽  
Mesenchymal Transition ◽  
Secretory Products

Eosinophilic esophagitis (EoE) is a recently recognized, immune-mediated disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. The chronic esophageal eosinophilia of EoE is associated with tissue remodeling that includes epithelial hyperplasia, subepithelial fibrosis, and hypertrophy of esophageal smooth muscle. This remodeling causes the esophageal rings and strictures that frequently complicate EoE and underlies the mucosal fragility that predisposes to painful mucosal tears in the EoE esophagus. The pathogenesis of tissue remodeling in EoE is not completely understood, but emerging studies suggest that secretory products of eosinophils and mast cells, as well as cytokines produced by other inflammatory cells, epithelial cells, and stromal cells in the esophagus, all contribute to the process. Interleukin (IL)-4 and IL-13, Th2 cytokines overproduced in allergic disorders, have direct profibrotic and remodeling effects in EoE. The EoE esophagus exhibits increased expression of transforming growth factor (TGF)-β1, which is a potent activator of fibroblasts and a strong inducer of epithelial-mesenchymal transition. In addition, IL-4, IL-13, and TGF-β all have a role in regulating periostin, an extracellular matrix protein that might influence remodeling by acting as a ligand for integrins, by its effects on eosinophils or by activating fibrogenic genes in the esophagus. Presently, few treatments have been shown to affect the tissue remodeling that causes EoE complications. This report reviews the potential roles of fibroblasts, eosinophils, mast cells, and profibrotic cytokines in esophageal remodeling in EoE and identifies potential targets for future therapies that might prevent EoE complications.

scholarly journals Prognostic and predictive significance of osteopontin in malignant neoplasms

2021 ◽  
Vol 8 (2) ◽  
pp. 23-28
Author(s):  
E. Yu. Zubareva ◽  
M. A. Senchukova
Keyword(s):  
Functional Role ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
Immunological Tolerance ◽  
Extracellular Matrix Protein ◽  
Malignant Neoplasms ◽  
Biological Processes ◽  
Mesenchymal Transition ◽  
Different Types ◽  
Integrated Study

Osteopontin is an extracellular matrix protein which is produced by different types of cells and plays an important functional role in many biological processes. This review discusses the main functions of osteopontin, its role in the progression and chemoresistance of malignant neoplasms, in the regulation of epithelial-mesenchymal transition, angiogenesis, and the body’s immune response to the tumor. The article considers the currently known mechanisms by which osteopontin affects to the survival, mobility and invasion of tumor cells, to tumor sensitivity to drug treatment, as well as the prospects for a integrated study of the predictive significance of osteopontin, markers of hypoxia, angiogenesis, epithelial- mesenchymal transition, and immunological tolerance.

lncRNA CTBP1-AS2 promotes proliferation and migration of glioma by modulating miR-370-3p–Wnt7a-mediated epithelial–mesenchymal transition

2020 ◽  
Vol 98 (6) ◽  
pp. 661-668
Author(s):  
Yongfeng Li ◽  
Jin Zong ◽  
Cong Zhao
Keyword(s):  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Assay ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
And Migration ◽  
Proliferation And Migration

Glioma is one of the most common and aggressive malignant primary brain tumors, with a poor 5-year survival rate. The long noncoding RNA (lncRNA) CTBP1-AS2 has been shown to be correlated with the prognosis of cancer, but the role of CTBP1-AS2 in glioma and its concrete mechanism is fully unknown. The clinical data and tissues of glioma patients were analyzed. Cell viability and migration assays were performed. Western blotting and qRT-PCR were adopted for investigation of target protein expressions. Double luciferase assay was used to investigate the interaction between different elements. The lncRNA CTBP1-AS2 had increased expression profiles in tumor tissues, which is associated with poor prognosis. In detail, CTBP1-AS2 knockdown decreased proliferation and migration phenotypes in both U87-MG and LN229 cells. Moreover, CTBP1-AS2 knockdown suppressed the key epithelial–mesenchymal transition (EMT) markers by downregulating Wnt7a-mediated signaling. Furthermore, miR-370-3p functioned as a link that could be absorbed by CTBP1-AS2, thus regulating Wnt7a expression. Lastly, the CTBP1-AS2–miR-370-3p–Wnt7a axis modulated EMT in glioma cells in vitro and in vivo. This study provides new insights that a novel lncRNA, CTBP1-AS2, regulates EMT of glioma by modulating the miR-370-3p–Wnt7a axis.

scholarly journals Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

2020 ◽  
Author(s):  
Lili Wang ◽  
Jingzhen Zhou ◽  
Yong Zhang ◽  
Tao Hu ◽  
Yongning Sun
Keyword(s):  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Gene Assay ◽  
Lncrna Neat1

Abstract Background: Previous studies have suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis in various human carcinomas, including osteosarcoma (OS). However, the expression and specific role of lncRNA NEAT1 in OS remain unknown. The current study aimed at revealing the role of lncRNA NEAT1 and its related mechanism in OS.Methods: Expression profiles of lncRNAs in OS tissues were constructed, and lncRNA NEAT1 expression was verified with RT-qPCR followed by sub-localization. LncRNA-microRNA (miRNA) and miRNA-mRNA interactions were predicted. Validation was performed using dual luciferase reporter gene assay, and gain- and loss-of-function experiments. The effects of lncRNA NEAT1, miR-579 and MMP13 on the proliferation, migration and invasion, epithelial-mesenchymal transition (EMT) of OS cells were detected using colony formation, cell counting kit-8 (CCK-8), Transwell assays and Western blot analysis.Results: LncRNA NEAT1 overexpression was observed in OS tissues and cell lines which located in the cytoplasm. Transfection-induced downregulation of lncRNA NEAT1/MMP13 or overexpression of miR-579 blocked the progression of OS cells. LncRNA NEAT1 promotes MMP13 through sponging miR-579.Conclusion: LncRNA NEAT1 might be beneficial for OS aggravation via sponging miR-579 and facilitating MMP13 expression, which represents a candidate marker and target for OS therapy.

scholarly journals Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Dismal Prognosis ◽  
Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

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