ArticleJournal of cancer research and clinical oncology2018
High MLL2 expression predicts poor prognosis and promotes tumor progression by inducing EMT in esophageal squamous cell carcinoma.
Article in Journal of cancer research and clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1.Oncogene · 2026Article
- Next generation sequencing identifies novel gene alterations with potential prognostic relevance in pediatric cancer: a single-center study.The oncologist · 2026Article
- Role of Coiled-Coil Domain-Containing Protein 86 in Tumorigenesis of Nasopharyngeal Carcinoma.Bulletin of experimental biology and medicine · 2025Article
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients.Future oncology (London, England) · 2024Article
- KMT2D links TGF-β signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity.International journal of cancer · 2023Article
- Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2023Article
- Roles of oncogenes in esophageal squamous cell carcinoma and their therapeutic potentials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Potential markers of cancer stem-like cells in ESCC: a review of the current knowledge.Frontiers in oncology · 2023Review
- Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma.Cell & bioscience · 2022Article
- The role of KMT2 gene in human tumors.Histology and histopathology · 2022Review
- Review
- Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors.Oncotarget · 2021Review
- Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene.BMC cancer · 2021Article
- Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells.Cancers · 2021Article
- CRISPR/Cas9 in Gastrointestinal Malignancies.Frontiers in cell and developmental biology · 2021Review
- Integrative Genomic Analyses of 1,145 Patient Samples Reveal New Biomarkers in Esophageal Squamous Cell Carcinoma.Frontiers in molecular biosciences · 2021Article
- Possible involvement of TGF‑β‑SMAD‑mediated epithelial‑mesenchymal transition in pro‑metastatic property of PAX6.Oncology reports · 2020Article
- EMT signaling: potential contribution of CRISPR/Cas gene editing.Cellular and molecular life sciences : CMLS · 2020Review
- Genetic mutational analysis of pediatric acute lymphoblastic leukemia from a single center in China using exon sequencing.BMC cancer · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMLL2 has been identified as one of the most frequently mutated genes in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, its clinical significance and prognostic value in ESCC has not been elucidated. In the present study, we aimed to investigate the expression and role of MLL2 in ESCC.
methodsImmunohistochemistry (IHC) and qRT-PCR were used to examine the expression profile of MLL2. Kaplan-Meier survival analysis and univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of MLL2 expression in Kazakh ESCC patients. Furthermore, to evaluate the biological function of MLL2 in ESCC, we applied the latest gene editing technique CRISPR/Cas9 to knockout MLL2 in ESCC cell line Eca109. MTT, colony formation, flow cytometry, scratch wound-healing and transwell migration assays were performed to investigate the effect of MLL2 on ESCC cell proliferation and migration. The correlation between MLL2 and epithelial-mesenchymal transition (EMT) was investigated by Western blot assay in vitro and IHC in ESCC tissue, respectively.
resultsBoth mRNA and protein expression levels of MLL2 were significantly overexpressed in ESCC patients. High expression of MLL2 was significantly correlated with TNM stage (P = 0.037), tumor differentiation (P = 0.032) and tumor size (P = 0.035). Kaplan-Meier survival analysis showed that patients with low MLL2 expression had a better overall survival than those with high MLL2 expression. Multivariate Cox analysis revealed that lymph node metastasis and tumor differentiation were independent prognostic factors. Knockout of MLL2 in Eca109 inhibited cell proliferation and migration ability, induced cell cycle arrest at G1 stage, but it had no significant effect on apoptosis. In addition, knockout of MLL2 could inhibit EMT by up-regulation of E-Cadherin and Smad7 as well as down-regulation of Vimentin and p-Smad2/3 in ESCC cells. In cancer tissues, the expression of E-Cadherin was negatively correlated with MLL2 expression while Vimentin expression was positively correlated with MLL2 expression.
conclusionOur results indicate that overexpression of MLL2 predicts poor clinical outcomes and facilitates ESCC tumor progression, and it may exert oncogenic role via activation of EMT. MLL2 may be used as a novel prognostic factor and therapeutic target for ESCC patients.
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