scholarly journals TET3- and OGT-Dependent Expression of Genes Involved in Epithelial-Mesenchymal Transition in Endometrial Cancer

2021 ◽  
Vol 22 (24) ◽  
pp. 13239
Author(s):  
Piotr Ciesielski ◽  
Paweł Jóźwiak ◽  
Ewa Forma ◽  
Anna Krześlak
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Tissue ◽  
Gene Expressions ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Ishikawa Cells

TET3 is a member of the TET (ten-eleven translocation) proteins family that catalyzes the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine. TET proteins can also affect chromatin modifications and gene expression independently of their enzymatic activity via interactions with other proteins. O-GlcNAc transferase (OGT), the enzyme responsible for modification of proteins via binding of N-acetylglucosamine residues, is one of the proteins whose action may be dependent on TET3. Here, we demonstrated that in endometrial cancer cells both TET3 and OGT affected the expression of genes involved in epithelial to mesenchymal transition (EMT), i.e., FOXC1, TWIST1, and ZEB1. OGT overexpression was caused by an increase in TWIST1 and ZEB1 levels in HEC-1A and Ishikawa cells, which was associated with increased O-GlcNAcylation of histone H2B and trimethylation of H3K4. The TET3 had the opposite effect on gene expressions and histone modifications. OGT and TET3 differently affected FOXC1 expression and the migratory potential of HEC-1A and Ishikawa cells. Analysis of gene expressions in cancer tissue samples from endometrial cancer patients confirmed the association between OGT or TET3 and EMT genes. Our results contribute to the knowledge of the role of the TET3/OGT relationship in the complex mechanism supporting endometrial cancer progression.

scholarly journals Roles of MicroRNA-34a in Epithelial to Mesenchymal Transition, Competing Endogenous RNA Sponging and Its Therapeutic Potential

2019 ◽  
Vol 20 (4) ◽  
pp. 861 ◽  
Author(s):  
Dongsong Nie ◽  
Jiewen Fu ◽  
Hanchun Chen ◽  
Jingliang Cheng ◽  
Junjiang Fu
Keyword(s):  
Cancer Therapy ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Circular Rna ◽  
Signal Pathways ◽  
Competing Endogenous Rna ◽  
Mesenchymal Transition

MicroRNA-34a (miR-34a), a tumor suppressor, has been reported to be dysregulated in various human cancers. MiR-34a is involves in certain epithelial-mesenchymal transition (EMT)-associated signal pathways to repress tumorigenesis, cancer progression, and metastasis. Due to the particularity of miR-34 family in tumor-associated EMT, the significance of miR-34a is being increasingly recognized. Competing endogenous RNA (ceRNA) is a novel concept involving mRNA, circular RNA, pseudogene transcript, and long noncoding RNA regulating each other’s expressions using microRNA response elements to compete for the binding of microRNAs. Studies showed that miR-34a is efficient for cancer therapy. Here, we provide an overview of the function of miR-34a in tumor-associated EMT. ceRNA hypothesis plays an important role in miR-34a regulation in EMT, cancer progression, and metastasis. Its potential roles and challenges as a microRNA therapeutic candidate are discussed. As the negative effect on cancer progression, miR-34a should play crucial roles in clinical diagnosis and cancer therapy.

scholarly journals Regulation of Epithelial-Mesenchymal Transition in Breast Cancer Cells by Cell Contact and Adhesion

2015 ◽  
Vol 14s3 ◽  
pp. CIN.S18965 ◽  
Author(s):  
Magdalena A. Cichon ◽  
Celeste M. Nelson ◽  
Derek C. Radisky
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Rna Splicing ◽  
Epithelial Mesenchymal Transition ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Cell Contact ◽  
Mesenchymal Transition ◽  
Matrix Metalloproteinase 3 ◽  
Expression Of Genes

Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development.

scholarly journals The Underappreciated Role of Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease and Its Strong Link to Lung Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1394
Author(s):  
Malik Quasir Mahmood ◽  
Shakti D. Shukla ◽  
Chris Ward ◽  
Eugene Haydn Walters
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
World Health ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition

The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality. The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression. Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking. In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions. We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer. As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications.

scholarly journals MiR-1301-3p Inhibits Epithelial to Mesenchymal Transition via Targeting RhoA in Pancreatic Cancer

2020 ◽  
Author(s):  
Xinxue Zhang ◽  
Xin Zhao ◽  
Junming Xu ◽  
Jun Ma ◽  
Zhe Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Pathological Differentiation

Abstract Background: Micro(mi)RNAs play an essential role in the epithelial-mesenchymal transition (EMT) process in human cancers. This study aimed to uncover the regulatory mechanism of miR-1301-3p on EMT in pancreatic cancer (PC).Methods: GEO database (GSE31568, GSE41372, and GSE32688) and the PC cohort of The Cancer Genome Atlas were applied to discover the expression and prognostic role of miR-1301-3p. In the validation cohort, qRT-PCR was performed in 72 paired PC tissue samples. CCK-8, wound healing, and transwell migration assays were used to detect miR-1301-3p function on PC cells. Luciferase reporter assays and western blotting were performed to discover the potential target of miR-1301-3p on EMT.Results: Our study revealed that miR-1301-3p was downregulated in PC tissues compared with normal samples. A low level of miR-1301-3p was associated with malignant pathological differentiation, lymphatic metastasis, tumor residual, and unsatisfactory overall survival. Gene Ontology analyses indicated that miR-1301-3p possibly regulated cell cycle and adheren junction. In vitro assays showed that miR-1301-3p suppressed proliferation, migration, and invasion ability of PC cells. Mechanically, miR-1301-3p inhibits RhoA expression, and knockdown of RhoA upregulated E-cadherin; however, downregulated N-cadherin and vimentin level.Conclusions: MiR-1301-3p acts as a prognostic biomarker for PC and inhibits PC progression by targeting RhoA induced EMT process.

scholarly journals Slug and Vimentin Downregulation at the Metastatic Site Is Associated With Skip-N2 Metastasis of Lung Adenocarcinoma

2022 ◽  
Author(s):  
Yasemin SAYGIDEGER ◽  
Alper AVCI ◽  
Emine BAGIR ◽  
Burcu SAYGIDEĞER DEMİR ◽  
Aycan SEZAN Ms ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
E Cadherin

Abstract Objective: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. Materials and Methods: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples.Results: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses.Conclusion: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

scholarly journals Histone methyltransferase SETD1A participates in lung cancer progression

2020 ◽  
Author(s):  
Mei Du ◽  
Piping Gong ◽  
Yun Zhang ◽  
Yanguo Liu ◽  
Xiaozhen Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Normal Lung ◽  
Control Group ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Cancer Symptoms ◽  
Mechanistic Analysis

Abstract Lung cancer is the leading cause of cancer-related death worldwide, with an estimated 1.2 million deaths each year. Despite advances in lung cancer treatment, 5-year survival rates are lower than ~15%, which is attributes to diagnosis limitations and current clinical drug resistance. Recently, more evidence has suggested that epigenome dysregulation is associated with the initiation and progress of cancer, and targeting epigenome-related molecules improves cancer symptoms. Interestingly, some groups reported that the level of methylation of histone 3 lysine 4 (H3K4me3) was increased in lung tumors and participated in abnormal transcriptional regulation. However, a mechanistic analysis is not available. In this report, we found that the SET domain containing 1A (SETD1A), the enzyme for H3K4me3, was elevated in lung cancer tissue compared to normal lung tissue. Knockdown of SETD1A in A549 and H1299 cells led to defects in cell proliferation and epithelial-mesenchymal transition (EMT), as evidenced by inhibited WNT and TGFβ pathways, compared with the control group. Xenograft assays also revealed a decreased tumor growth and EMT in the SETD1A silenced group compared with the control group. Mechanistic analysis suggested that SETD1A might regulate tumor progression via several critical oncogenes, which exhibited enhanced H3K4me3 levels around transcriptional start sites in lung cancer. This study illustrates the important role of SETD1A in lung cancer and provides a potential drug target for treatment.

A Hidden Human Proteome Signature Characterizes the Epithelial Mesenchymal Transition Program

2020 ◽  
Vol 26 (3) ◽  
pp. 372-375 ◽  
Author(s):  
Daniele Vergara ◽  
Tiziano Verri ◽  
Marina Damato ◽  
Marco Trerotola ◽  
Pasquale Simeone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Open Reading Frames ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Cellular Models ◽  
Genomic Regions ◽  
Protein Signature

Background: Molecular changes associated with the initiation of the epithelial to mesenchymal transition (EMT) program involve alterations of large proteome-based networks. The role of protein products mapping to non-coding genomic regions is still unexplored. Objective: The goal of this study was the identification of an alternative protein signature in breast cancer cellular models with a distinct expression of EMT markers. Methods: We profiled MCF-7 and MDA-MB-231 cells using liquid-chromatography mass/spectrometry (LCMS/ MS) and interrogated the OpenProt database to identify novel predicted isoforms and novel predicted proteins from alternative open reading frames (AltProts). Results: Our analysis revealed an AltProt and isoform protein signature capable of classifying the two breast cancer cell lines. Among the most highly expressed alternative proteins, we observed proteins potentially associated with inflammation, metabolism and EMT. Conclusion: Here, we present an AltProts signature associated with EMT. Further studies will be needed to define their role in cancer progression.

scholarly journals Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

2015 ◽  
Vol 37 (4) ◽  
pp. 1503-1512 ◽  
Author(s):  
Yinghua Li ◽  
Yunpeng Xie ◽  
Dan Cui ◽  
Yanni Ma ◽  
Linlin Sui ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Related Factors ◽  
Western Blots ◽  
Mesenchymal Transition ◽  
Novel Target

Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.

scholarly journals Histone methyltransferase SETD1A participates in lung cancer progression

2020 ◽  
Author(s):  
Mei Du ◽  
Xiuwen Wang ◽  
Piping Gong ◽  
Yun Zhang ◽  
Yanguo Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Normal Lung ◽  
Control Group ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Cancer Symptoms ◽  
Mechanistic Analysis

Abstract Lung cancer is the leading cause of cancer-related death worldwide, with an estimated 1.2 million deaths each year. Despite advances in lung cancer treatment, 5-year survival rates are lower than ~ 15%, which is attributed to diagnosis limitations and current clinical drug resistance. Recently, more evidence has suggested that epigenome dysregulation is associated with the initiation and progress of cancer, and targeting epigenome-related molecules improves cancer symptoms. Interestingly, some groups reported that the level of methylation of histone 3 lysine 4 (H3K4me3) was increased in lung tumors and participated in abnormal transcriptional regulation. However, a mechanistic analysis is not available. In this report, we found that the SET domain containing 1A (SETD1A), the enzyme for H3K4me3, was elevated in lung cancer tissue compared to normal lung tissue. Knockdown of SETD1A in A549 and H1299 cells led to defects in cell proliferation and epithelial-mesenchymal transition (EMT), as evidenced by inhibited WNT and TGFβ pathways, compared with the control group. Xenograft assays also revealed a decreased tumor growth and EMT in the SETD1A silenced group compared with the control group. Mechanistic analysis suggested that SETD1A might regulate tumor progression via several critical oncogenes, which exhibited enhanced H3K4me3 levels around transcriptional start sites in lung cancer. This study illustrates the important role of SETD1A in lung cancer and provides a potential drug target for treatment.

Sign in / Sign up

Export Citation Format

Share Document