UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis

Huang, Zhong-Feng; Tang, Yu-Ling; Shen, Zhaolong; Yang, Kehu; Gao, Kai

doi:10.1016/j.omto.2021.12.008

Cited by 15 publications

(20 citation statements)

References 29 publications

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“…Unlike the nuclear protein UXT-V2 which has multi-functions in prostate cancer [35,36], breast cancer [37,38], clear cell renal cell carcinoma [39], and CRC [40], the function of cytoplasmic UXT-V1 has largely unknown. In addition to the role in TNFα-induced apoptosis [9] and innate antiviral signal transduction [41], we have found UXT-V1 is highly expressed in cancer tissues in clinical specimens from CRC patients.…”

Section: Discussionmentioning

confidence: 99%

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Chen

Xiao

et al. 2023

Preprint

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Background: Colorectal cancer (CRC) is one of malignant tumors that seriously threatening human health. β-catenin is a central hub in Wnt pathway, aberrant activation of Wnt/β-catenin signaling pathway promotes the tumorigenesis/progression of CRC. Methods and Results: Here we found a β-catenin interactor, UXT-V1, could modulate Wnt signaling. The expression of UXT-V1 mRNA was increased in CRC tissues. Overexpression of UXT-V1 increased the canonical Wnt signaling, as evidenced by Wnt reporter systems and the up-regulation of marker genes including Axin, CyclinD1 and c-Myc. While, knockdown of UXT-V1 impaired the expression of these genes and attenuated Wnt signaling. Mechanistically, overexpression of UXT-V1 could inhibit GSK3β mediated β-catenin phosphorylation and degradation. Knockout of UXT-V1 increased β-catenin phosphorylation, prevented CRC cell growth, and inhibited tumorigenesis in NOD-SCID mice. Conclusions: Taken together, our findings revealed that UXT-V1 could control Wnt signaling through targeting GSK3β mediated β-catenin phosphorylation and degradation, providing a molecular basis for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Chen

Xiao

et al. 2023

Preprint

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“…Glioma growth is slowed in vitro and in vivo experiments when a DNMT1 inhibitor is given ( 36 ). Currently, there is no specific research on DNMT3B in glioma, but DNMT3B has been reported to accelerate the occurrence and progression of esophageal cancer ( 38 ), lung cancer ( 39 ), breast cancer ( 40 ), and ovarian cancer ( 41 ), implying that DNMT3B is an essential biomarker in cancer pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of m6A/m5C/m1A-related gene expression, immune infiltration, and sensitivity of antineoplastic drugs in glioma

Zhao

Wen-hu²,

Yang³

et al. 2022

Front. Immunol.

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This research aims to develop a prognostic glioma marker based on m6A/m5C/m1A genes and investigate the potential role in the tumor immune microenvironment. Data for patients with glioma were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The expression of genes related to m6A/m5C/m1A was compared for normal and glioma groups. Gene Ontology and Kyoto Encyclopedia of Genes and Gene enrichment analysis of differentially expressed genes were conducted. Consistent clustering analysis was performed to obtain glioma subtypes and complete the survival analysis and immune analysis. Based on TCGA, Lasso regression analysis was used to obtain a prognostic model, and the CGGA database was used to validate the model. The model-based risk scores and the hub genes with the immune microenvironment, clinical features, and antitumor drug susceptibility were investigated. The clinical glioma tissues were collected to verify the expression of hub genes via immunohistochemistry. Twenty genes were differentially expressed, Consensus cluster analysis identified two molecular clusters. Overall survival was significantly higher in cluster 2 than in cluster 1. Immunological analysis revealed statistically significant differences in 26 immune cells and 17 immune functions between the two clusters. Enrichment analysis detected multiple meaningful pathways. We constructed a prognostic model that consists of WTAP, TRMT6, DNMT1, and DNMT3B. The high-risk and low-risk groups affected the survival prognosis and immune infiltration, which were related to grade, gender, age, and survival status. The prognostic value of the model was validated using another independent cohort CGGA. Clinical correlation and immune analysis revealed that four hub genes were associated with tumor grade, immune cells, and antitumor drug sensitivity, and WTAP was significantly associated with microsatellite instability(MSI). Immunohistochemistry confirmed the high expression of WTAP, DNMT1, and DNMT3B in tumor tissue, but the low expression of TRMT6. This study established a strong prognostic marker based on m6A/m5C/m1A methylation regulators, which can accurately predict the prognosis of patients with gliomas. m6A/m5C/m1A modification mode plays an important role in the tumor microenvironment, can provide valuable information for anti-tumor immunotherapy, and have a profound impact on the clinical characteristics.

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“…The overexpression of MEG3 markedly increased the p53 protein level and stimulated p53-dependent transcription from a p53-responsive promoter [ 46 ]. Another study indicated that the overexpression of MEG3 increased both mRNA and protein levels of p53 in MCF-7 and ZR75-1 breast cancer cells [ 47 ]. Deletion mutations of MEG3 failed to stimulate p53 transcriptional activity, suggesting that the full length of MEG3 was required for p53 transcription [ 47 ].…”

Section: Meg3mentioning

confidence: 99%

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

Zhang

Shi

et al. 2023

Toxics

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Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.

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UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis

Cited by 15 publications

References 29 publications

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Comprehensive analysis of m6A/m5C/m1A-related gene expression, immune infiltration, and sensitivity of antineoplastic drugs in glioma

Long Non-Coding RNA MEG3 in Metal Carcinogenesis

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