MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B

Hong, Xuehui; Yang, Xu; Qiu, Xingfeng; Zhu, Yuekun; Feng, Xing; Ding, Zhijie; Zhang, Shifeng; Zhong, Lifeng; Zhuang, Yifan; Su, Chen; Hong, Xuemin; Cai, Jun

doi:10.18632/oncotarget.8020

Cited by 41 publications

(29 citation statements)

References 19 publications

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“…It has been reported that deletion of G-protein-coupled receptor-48 (GPR48) led to decreased expression of KDM2B through cAMP-CREB pathway [49]. Furthermore, miR-448 and miR-146a-5p could also regulate the expression of KDM2B [50,51]. However, the mechanism of increased expression of KDM2B in PDAC has not been revealed, which could be further studied.…”

Section: Discussionmentioning

confidence: 99%

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Quan

Chen

Jiao

et al. 2020

J Exp Clin Cancer Res

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Background: Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. Methods: The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. Results: We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. Conclusion: This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.

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Section: Discussionmentioning

confidence: 99%

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Quan

Chen

Jiao

et al. 2020

J Exp Clin Cancer Res

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“…Among them, the JmjC domain is the active center that can catalyze the demethylation of H3K36me2 and H3K4me3 28–31. Recently, some studies have suggested that KDM2B regulates gene expression in a JmjC-dependent manner and may be involved in tumorigenesis; thus, it has gradually received increasing research attention 25,32. KDM2B overexpression in mouse embryonic fibroblasts (MEFs) induces cellular proliferation and inhibits apoptosis, leading to the immortalization of normal cells 7…”

Section: Discussionmentioning

confidence: 99%

Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression and contributes to the progression of ovarian cancer in vitro and in vivo

Guo

et al. 2017

OTT

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Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms. To determine the expression pattern of KDM2B in ovarian neoplasms, we analyzed the mRNA and protein levels of KDM2B and the histone methyltransferase enhancer of zester homolog 2 (EZH2) in normal, benign, borderline, and malignant ovarian tissue samples. We found that KDM2B expression was gradually increased in ovarian tumors, with the highest expression found in the malignant ovarian tissues, and the differences in KDM2B expression among the different International Federation of Gynecology and Obstetrics stages and pathological grades/types were statistically significant. Moreover, KDM2B expression was positively correlated with EZH2 expression in ovarian tissues. To determine the role of KDM2B in tumorigenesis in vitro and in vivo, we silenced KDM2B expression in ovarian cancer cells using the KDM2B short hairpin RNA expression lentivirus and established a nude mouse xenograft model. Downregulation of endogenous KDM2B decreased the expression of EZH2 and reduced the proliferation and migration of ovarian cancer cells. Loss of KDM2B suppressed ovarian tumor formation in vivo. Our results suggest that KDM2B plays an important role in the tumorigenesis of ovarian cancer, with a possible mechanism of increasing the expression of the oncogene EZH2; this indicates that certain histone methyltransferase may be positively regulated by certain histone demethylase in the epigenetic regulation of ovarian tumors. KDM2B may be a novel therapeutic target for the clinical treatment of ovarian cancer.

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“…If abnormal JmjC demethylase activity is modulated, it can lead to normal transcriptional arrangements. Therefore, JmjC domain inhibitors might have therapeutic potentials for the treatment of cancer [24,25,26,27].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potentials of İnhibition Jumonji C Domain Containing Demethylases in Acute Myeloid Leukemia

Koca

Hastar

Engür

et al. 2019

Tjh

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Objective: Acute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases. Materials and Methods:The cytotoxic and apoptotic effects of methylstat and doxorubicin on HL-60 cells were detected by MTT cell viability assay, double staining of treated cells with annexin-V/ propidium iodide, and caspase-3 activity assay. Mitochondrial activity was analyzed using JC-1 dye. The expression levels of the BCL2 and BCL2L1 anti-apoptotic genes in HL-60 cells were determined using real-time polymerase chain reaction (PCR). Lastly, the cytostatic effect was determined by cell cycle analysis. Results:In our research, cytotoxic, cytostatic, and apoptotic effects of methylstat on human HL-60 cells were investigated. Cytotoxic and cytostatic analyses revealed that methylstat decreased cell proliferation in a dose-dependent cytotoxic manner and arrested HL-60 cells in the G2/M and S phases. Methylstat also induced apoptosis through the loss of mitochondrial membrane potential and increases in caspase-3 enzyme activity. The expression levels of BCL2 and BCL2L1 were also decreased according to real-time PCR results. Finally, the combination of methylstat with doxorubicin resulted in synergistic cytotoxic effects on HL-60 cells. Conclusion:Taken together, these results demonstrate that methylstat may be a powerful candidate as a drug component of AML treatment protocols.

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MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B

Cited by 41 publications

References 19 publications

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression and contributes to the progression of ovarian cancer in vitro and in vivo

Therapeutic Potentials of İnhibition Jumonji C Domain Containing Demethylases in Acute Myeloid Leukemia

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