CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells

Song, Xin; Wu, Ning; Niu, Jin-wei; Zhang, Guochao; Liu, Haibin; Zhou, Lei

doi:10.1007/s13577-020-00477-w

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…Thus, it is important to investigate the role of miR-378a-3p in regulating HCC angiogenesis to develop therapeutic interventions. Several studies have shown that miR-378a-3p plays different functions in different tumors [23,[36][37][38][39][40]. In this study, we found that the expression of miR-378a-3p was downregulated in HCC and was related to the poor prognosis.…”

Section: Discussionmentioning

confidence: 49%

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

Zhu

Chen

Feng

et al. 2021

Preprint

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Background: Angiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). miR-378a-3p participates in tumorigenesis and tumor metastasis according to previous studies, yet the exact role it plays in HCC angiogenesis remains poorly understood.Methods: qRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by CCK-8, transwell assay, tube formation and matrigel plug assay. RNA sequencing, bioinformatics analysis, luciferase reporter assay, immunofluorescence assay and ChIP assay were used to detected the molecular mechanism of miR-378a-3p-induced inhibition of angiogenesis. Results: We confirmed that the expression of miR-378a-3p was significantly downregulated and was associated with microvascular density (MVD) in HCC, which indicated a short survival time of HCC patients, and reducing miR-378a-3p expression led to a significant increase in angiogenesis in vitro and in vivo. miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then decreases secreted vascular endothelial growth factor (VEGF). DNA methyltransferase 1 (DNMT1) mediated hypermethylation of miR-378a-3p was responsible for downregulating of miR-378a-3p. Moreover, a series of investigation indicated that p65 initiated a positive feedback loop, which could up-regulate DNMT1 to promote hypermethylation of the miR-133a-3p promoter.Conclusion: Our study indicates that a novel DNMT1/miR-378a-3p/TRAF1/ NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 49%

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

Zhu

Chen

Feng

et al. 2021

Preprint

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“… 86 Similarly, CBX8 knockdown in CRC cell lines reduces cell viability and tumor xenografts in mice, likely via affecting p53-signaling. 87 , 88 In contrast to CBX2/8, CBX4 appears to have a tumor-inhibitory functions as its overexpression in the CRC cell line DLD1 reduces cell migration, while knockdown of CBX4 in HCT116 cells increases tumor size and metastases. Here, downregulation of RUNX2 , a pro-metastatic marker in CRC, by the CBX4-HDAC3 complex was proposed as a potential mechanism behind the anti-tumor function of CBX4 in CRC.…”

Section: Mainmentioning

confidence: 99%

The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer

Larue,

Atlasi

2024

Stem Cells

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Epigenetic mechanisms play a pivotal role in controlling gene expression and cellular plasticity in both normal physiology and pathophysiological conditions. These mechanisms are particularly important in the regulation of stem cell self-renewal and differentiation, both in embryonic development and within adult tissues. A prime example of this finely tuned epigenetic control is observed in the gastrointestinal lining, where the small intestine undergoes renewal approximately every 3-5 days. How various epigenetic mechanisms modulate chromatin functions in intestinal stem cells (ISCs) is currently an active area of research. In this review, we discuss the main epigenetic mechanisms that control ISC differentiation under normal homeostasis. Furthermore, we explore the dysregulation of these mechanisms in the context of colorectal cancer (CRC) development. By outlining the main epigenetic mechanisms contributing to CRC, we highlight the recent therapeutics development and future directions for colorectal cancer research.

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“…CBX8 may inhibit the nuclear output of premiR-378a depending on its own nuclear localization and interaction with premiR-378a, thus inhibiting the maturation of miR-378a. MiR-378a-3p inhibits the malignant expression of human CC cells by targeting protein disulfide-isomerase A4, resulting in an increase in caspase-3 and caspase-7 activity (186). MiR-429 targets CBX8 to promote apoptosis in DLBCL (187).…”

Section: Cbxs Regulate Biological Tumor Processes Through Epigenetic ...mentioning

confidence: 99%

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

et al. 2023

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Chromobox (CBX) proteins are important epigenetic regulatory proteins and are widely involved in biological processes, such as embryonic development, the maintenance of stem cell characteristics and the regulation of cell proliferation and apoptosis. Disorder and dysfunction of CBXs in cancer usually lead to the blockade or ectoptic activation of developmental pathways, promoting the occurrence, development and progression of cancer. In the present review, the characteristics and functions of CBXs were first introduced. Subsequently, the expression of CBXs in cancers and the relationship between CBXs and clinical characteristics (mainly cancer grade, stage, metastasis and relapse) and prognosis were discussed. Finally, it was described how CBXs regulate cell proliferation and self-renewal, apoptosis and the acquisition of malignant phenotypes, such as invasion, migration and chemoresistance, through mechanisms involving epigenetic modification, nuclear translocation, noncoding RNA interactions, transcriptional regulation, posttranslational modifications, protein-protein interactions, signal transduction and metabolic reprogramming. The study also focused on cancer therapies targeting CBXs. The present review provides new insight and a comprehensive basis for follow-up research on CBXs and cancer. Contents1. Introduction 2. Constituent members of CBXs 3. Characteristics and functions of PcG family CBXs 4. Characteristics and functions of HP1 family CBXs 5. Expression of CBXs in cancers and the relationship between CBXs and clinical characteristics and prognosis 6. CBXs regulate biological tumor processes through epigenetic modification, nuclear translocation, ncRNA interactions, transcriptional regulation, PTMs, proteinprotein interactions, signal transduction and metabolic reprogramming 7. Cancer therapies targeting CBXs 8. Conclusion and prospects

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CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells

Cited by 7 publications

References 24 publications

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

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