Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice

Folic acid (FA) intake has been associated with increased breast cancer risk in some studies. Although underlying mechanisms are unknown, epigenetic modifications that persistently alter transcription have been suggested. We tested the hypothesis that high FA (HFA) intake alters the adult mammary transcriptome in a manner consistent with increased potential for carcinogenesis, detectable beyond the period of intake. C57BL/6 mice were fed control FA (CFA) (1 mg/kg diet) or HFA (5 mg/kg diet) diets for 4 weeks, followed by AIN93M maintenance diet for 4 weeks. Plasma 5-methyltetrahydrofolate, p-aminobenzoylglutamate and unmetabolised FA concentrations were greater (1.62, 1.56, 5.80-fold, respectively) in HFA compared to CFA mice. RNA sequencing of the mammary transcriptome (~20 million reads) showed 222 transcripts (191 upregulated) differentially expressed between groups. Gene Set Enrichment showed upregulated genes significantly enriched in Epithelial Mesenchymal Transition, Myogenesis and Apical Junction and downregulated genes in E2F targets, MYC targets and G2M checkpoint. Cancer was the most altered Disease and Disorder pathway, with Metastasis, Mammary Tumour and Growth of Tumour the most upregulated pathways. ChIP-seq enrichment analysis showed that targets of histone methyltransferase EZH2 were enriched in HFA mice. This study demonstrates HFA intake during adulthood induces mammary transcriptome changes, consistent with greater tumorigenic potential.

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Identification of Epithelial–Mesenchymal Transition-Related Prognostic lncRNAs Biomarkers Associated With Melanoma Microenvironment

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.679133 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bo Xiao ◽

Liyan Liu ◽

Zhuoyuan Chen ◽

Aoyu Li ◽

Pingxiao Wang ◽

...

Keyword(s):

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Enrichment Analysis ◽

Roc Curves ◽

Risk Groups ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Kaplan Meier

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.

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Tiny miRNAs Play a Big Role in the Treatment of Breast Cancer Metastasis

Cancers ◽

10.3390/cancers13020337 ◽

2021 ◽

Vol 13 (2) ◽

pp. 337

Author(s):

Andrea York Tiang Teo ◽

Xiaoqiang Xiang ◽

Minh TN Le ◽

Andrea Li-Ann Wong ◽

Qi Zeng ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Tumour Progression ◽

Tumour Microenvironment ◽

Breast Cancer Metastasis ◽

Metastatic Progression ◽

Mesenchymal Transition ◽

Recent Developments ◽

Underlying Mechanisms

Distant organ metastases accounts for the majority of breast cancer deaths. Given the prevalence of breast cancer in women, it is imperative to understand the underlying mechanisms of its metastatic progression and identify potential targets for therapy. Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of tumour progression and metastasis in various cancers, playing either oncogenic or tumour suppressor roles. In the following review, we discuss the roles of miRNAs that potentiate four key areas of breast cancer metastasis—angiogenesis, epithelial-mesenchymal transition, the Warburg effect and the tumour microenvironment. We then evaluate the recent developments in miRNA-based therapies in breast cancer, which have shown substantial promise in controlling tumour progression and metastasis. Yet, certain challenges must be overcome before these strategies can be implemented in clinical trials.

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LncRNA FBXL19-AS1 promotes breast cancer cells proliferation and invasion via acting as a molecular sponge to miR-718

Bioscience Reports ◽

10.1042/bsr20182018 ◽

2019 ◽

Vol 39 (4) ◽

Cited By ~ 7

Author(s):

Zhenmin Ding ◽

Pengcheng Ye ◽

Xiaohu Yang ◽

Hongmiao Cai

Keyword(s):

Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Potential Therapeutic Target ◽

Poor Overall Survival ◽

Mesenchymal Transition ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

Proliferation And Invasion

Abstract Long non-coding RNAs (lncRNAs) have been suggested to serve vital roles in tumor initiation and progression. However, the expression and underlying mechanisms of lncRNA FBXL19-AS1 in breast cancer (BC) remain unclear. In the present study, we found that FBXL19-AS1 expression was significantly up-regulated and correlated with advanced clinical features and poor overall survival of BC patients. Functionally, FBXL19-AS1 inhibition suppressed BC cells proliferation, invasion, and epithelial–mesenchymal transition (EMT) processes in vitro and reduced tumor growth in vivo. In addition, we found that FBXL19-AS1 might function as a ceRNA to sponge miR-718, and miR-718 could rescue the effects of FBXL19-AS1 on BC cells progression. Therefore, these findings suggested that FBXL19-AS1 might serve as an oncogenic lncRNA and promoted BC progression by sponging miR-718, indicating FBXL19-AS1 could serve as a potential therapeutic target for BC treatment.

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Identification of An Epithelial-Mesenchymal Transition-Related lncRNA Prognostic Signature For Patients With Glioblastoma

10.21203/rs.3.rs-820534/v1 ◽

2021 ◽

Author(s):

XinJie Yang ◽

Sha Niu ◽

JiaQiang Liu ◽

ZeYu Wu ◽

Shizhang Ling ◽

...

Keyword(s):

High Risk ◽

Signaling Pathways ◽

Epithelial Mesenchymal Transition ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Prognostic Signature ◽

Mesenchymal Transition ◽

Underlying Mechanisms

Abstract Purpose: Glioblastoma (GBM) is a class of strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis and progression of GBM through regulation of various cancer-related genes and signaling pathways. Here, we aimed to establish an epithelial-mesenchymal transition (EMT)-related lncRNA signature for GBM and explore its underlying mechanisms. Methods: Differential expression analysis and Gene set enrichment analysis (GSEA) were performed to explore key genes and signaling pathways associated with GBM. Spearman correlation analysis, Univariate and multivariate Cox regression analyses were used to construct a lncRNA prognostic signature for GBM patients. Kaplan-Meier analysis and receiver-operating-characteristic (ROC) analysis were applied to assess the performance of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses were performed to explore the underlying mechanisms of the signature. Single-sample GSEA (ssGSEA) was employed to explore the relationship of the signature and immune activities in GBM.Results: We focused on the essential role of EMT in GBM and identified 78 upregulated EMT-related genes in GBM. A total of 301 EMT-related lncRNAs were confirmed in GBM and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established, which could divide GBM patients into low- and high-risk subgroups. The accuracy and efficiency of the signature were validated to be satisfactory. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we found the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. Conclusion: we established an effective and robust EMT-related lncRNA signature which is expected to predict the prognosis and immunotherapy response for GBM patients.

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Co-regulation of alternative splicing by hnRNPM and ESRP1 during EMT

10.1101/301267 ◽

2018 ◽

Author(s):

Samuel E. Harvey ◽

Yilin Xu ◽

Xiaodan Lin ◽

Xin D. Gao ◽

Yushan Qiu ◽

...

Keyword(s):

Breast Cancer ◽

Alternative Splicing ◽

Cancer Metastasis ◽

Developmental Process ◽

Epithelial Mesenchymal Transition ◽

Enrichment Analysis ◽

Mesenchymal Transition ◽

Cancer Subtypes ◽

Functional Relationships ◽

Splicing Regulators

ABSTRACTThe epithelial-mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome-scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they co-regulate a set of cassette exon events, with the majority showing discordant splicing regulation. hnRNPM discordantly regulated splicing events show a positive correlation with splicing during EMT while concordant splicing events do not, highlighting the antagonistic role of hnRNPM and ESRP1 during EMT. Motif enrichment analysis near co-regulated exons identifies guanine-uridine rich motifs downstream of hnRNPM-repressed and ESRP1-enhanced exons, supporting a model of competitive binding to these cis-elements to antagonize alternative splicing. The set of co-regulated exons are enriched in genes associated with cell-migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of co-regulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtypes. These data identify complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts.

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