scholarly journals TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in Glioblastoma multiforme

2021 ◽  
Author(s):  
Lee Admoni-Elisha ◽  
Michal Feldman ◽  
Tzofit Elbaz ◽  
Anand Chopra ◽  
Guy Shapira ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Glioblastoma Multiforme ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Helix Loop Helix ◽  
Non Coding Rna ◽  
Cell Adhesion And Migration ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Repressive H3k27me3 Mark

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor among adults, which is characterized by high invasion, migration and proliferation abilities. One important process that contributes to the invasiveness of GBM is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in GBM patients. RNA-seq analysis in U251 GBM cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby suppressing EMT in GBM. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.

scholarly journals Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ramkrishna Mitra ◽  
Xi Chen ◽  
Evan J. Greenawalt ◽  
Ujjwal Maulik ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals LINC00084/miR-204/ZEB1 Axis Mediates Myofibroblastic Differentiation Activity in Fibrotic Buccal Mucosa Fibroblasts: Therapeutic Target for Oral Submucous Fibrosis

2021 ◽  
Vol 11 (8) ◽  
pp. 707
Author(s):  
Yu-Hsien Lee ◽  
Yi-Wen Liao ◽  
Ming-Yi Lu ◽  
Pei-Ling Hsieh ◽  
Cheng-Chia Yu
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Oral Submucous Fibrosis ◽  
Collagen Gel ◽  
Luciferase Reporter ◽  
Areca Nut ◽  
Mesenchymal Transition ◽  
Collagen Gel Contraction ◽  
Non Coding Rna ◽  
Submucous Fibrosis ◽  
Long Non Coding Rna

Oral submucosal fibrosis (OSF) is a precancerous condition in the oral cavity and areca nut consumption has been regarded as one of the etiologic factors implicated in the development of OSF via persistent activation of buccal mucosal fibroblasts (BMFs). It has been previously reported that an epithelial to mesenchymal transition (EMT) factor, ZEB1, mediated the areca nut-associated myofibroblast transdifferentiation. In the current study, we aimed to elucidate how areca nut affected non-coding RNAs and the subsequent myofibroblast activation via ZEB1. We found that long non-coding RNA LINC00084 was elicited in the BMFs treated with arecoline, a major alkaloid of areca nut, and silencing LINC00084 prevented the arecoline-induced activities (such as collagen gel contraction, migration, and wound healing capacities). The upregulation of LINC00084 was also observed in the OSF tissues and fibrotic BMFs (fBMFs), and positively correlated with several fibrosis factors. Moreover, we showed knockdown of LINC00084 markedly suppressed the myofibroblast features in fBMFs, including myofibroblast phenotypes and marker expression. The results from the luciferase reporter assay confirmed that LINC00084 acted as a sponge of miR-204 and miR-204 inhibited ZEB1 by directly interacting with it. Altogether, these findings suggested that the constant irritation of arecoline may result in upregulation of LINC00084 in BMFs, which increased the ZEB1 expression by sequestering miR-204 to induce myofibroblast transdifferentiation.

Truncation of MYH8 tail in AML: a novel prognostic marker with increase cell migration and epithelial–mesenchymal transition utilizing RAF/MAPK pathway

2019 ◽  
Vol 41 (6) ◽  
pp. 817-827 ◽  
Author(s):  
Hyejoo Park ◽  
Daeyoon Kim ◽  
Dongchan Kim ◽  
Jihyun Park ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Prognostic Marker ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Mapk Pathway ◽  
Adhesion Assay ◽  
Genome Database ◽  
Mesenchymal Transition ◽  
Cell Adhesion And Migration ◽  
And Migration

Abstract MYH8 is an actin-based motor protin involved in integrin-mediated cell adhesion and migration. Heretofore, the association of MYH8 mutation and cancer is unclear. In this study, we investigated the biologic significance of novel MYH8 tail truncation mutation, R1292X, in acute myeloid leukemia (AML) which was discovered by whole-exome sequencing and targeted re-sequencing of 209 AML patients. The patients harboring the mutation all relapsed within 3.8–20.9 months. To explore the functional consequence of the mutation in AML progress, we established knock-in cell lines using CRISPR-Cas9 genome editing. Using the established mutant model, we assessed traits of cancer progress. The mutant cells had improved motility, which was confirmed by immunofluorescence staining, wound healing, transwell migration and adhesion assay. The cell morphology and cell cycle were altered to be accessible to migration and epithelial-to-mesenchymal transition (EMT) transcription factors were also increased. The Raf and p44/42 MAPK pathway was a major regulator of these characteristics proved by a screening of signal transduction and inhibitor assay. Further, a public cancer genome database (cBioPortal) shows that MYH8 tail truncation mutations occurring near the R1292 position of the genome may have a significant function in cancer. In conclusion, truncation of MYH8 could be a novel prognostic marker related to poor prognosis by inducing cell migration and EMT features, and inhibition of the Raf/MAPK pathway would be a therapeutic strategy for AML patients with MYH8 tail truncation.

scholarly journals Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1802 ◽  
Author(s):  
Qi-Yuan Huang ◽  
Guo-Feng Liu ◽  
Xian-Ling Qian ◽  
Li-Bo Tang ◽  
Qing-Yun Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Regulatory Effects ◽  
Long Non Coding Rna

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

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