Growth Inhibition Accompanied by MOB1 Upregulation in Human Acute Lymphoid Leukemia Cells by 3-Deazaneplanocin A

Shen, Jianzhen; Su, Junnan; Wu, Dansen; zhang, Feng; Fu, Haiying; Zhou, Huarong; Xu, Meihong

doi:10.1007/s10528-015-9688-7

Cited by 7 publications

(11 citation statements)

References 35 publications

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“…It has been reported that ubiquitin ligase praja2 led to proteolysis of MOB1 in glioblastoma [18]. In acute lymphoid leukemia cells, CpG DNA methylation in MOB1 promoters inhibited the expression of MOB1 gene [37]. In PDAC, miRNA-181c directly bound to the 3'UTR region of MOB1 transcripts and inhibited the expression level [46].…”

Section: Discussionmentioning

confidence: 99%

“…We further studied the regulatory mechanisms of MOB1 in PDAC. It has been reported that CpG mehtylation was detected in MOB1 promoter [37]. Thus, we incubated PANC-1, AsPC-1 and MiaPaca-2 cell lines with the demethylating agent 5-azacytidine (5-aza) for 72 h and western blot was used to test the protein levels of MOB1.…”

Section: Kdm2b Binding To the Promoter Region And Transcriptionally Smentioning

confidence: 99%

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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%

Section: Kdm2b Binding To the Promoter Region And Transcriptionally Smentioning

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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“…By studying the effects of 3-deazaneplanocin A (DZNep), a histone methyltransferase EZH2 inhibitor, on human T-cell acute lymphoid leukaemia (T-ALL) cells, Shen et al found that DZNep treatment reduced histone methylation in hMOB1 promoters, resulting in an upregulation of hMOB1 expression associated with inhibited growth of T-ALL cells [156]. Thus, MOB1 levels may represent an indicative marker for DZNep treatments of T-ALL patients.…”

Section: Mobs and Cancermentioning

confidence: 99%

MOB (Mps one Binder) Proteins in the Hippo Pathway and Cancer

Gündoğdu

Hergovich

2019

Cells

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The family of MOBs (monopolar spindle-one-binder proteins) is highly conserved in the eukaryotic kingdom. MOBs represent globular scaffold proteins without any known enzymatic activities. They can act as signal transducers in essential intracellular pathways. MOBs have diverse cancer-associated cellular functions through regulatory interactions with members of the NDR/LATS kinase family. By forming additional complexes with serine/threonine protein kinases of the germinal centre kinase families, other enzymes and scaffolding factors, MOBs appear to be linked to an even broader disease spectrum. Here, we review our current understanding of this emerging protein family, with emphases on post-translational modifications, protein-protein interactions, and cellular processes that are possibly linked to cancer and other diseases. In particular, we summarise the roles of MOBs as core components of the Hippo tissue growth and regeneration pathway.

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“…Epigenetic agent 3-Deazaneplanocin A is an inhibitor of S-adenosyl-L-methionine-dependent HMTs, including EZH2. In preclinical studies, it was shown to inhibit cell proliferation and cause apoptosis in various cancer types [11, 12].…”

Section: Introductionmentioning

confidence: 99%

HDAC and HMT Inhibitors in Combination with Conventional Therapy: A Novel Treatment Option for Acute Promyelocytic Leukemia

Vitkevičienė

Skiauterytė

Žučenka

et al. 2019

Journal of Oncology

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Acute promyelocytic leukemia (APL) is characterized by PML-RARA translocation, which causes the blockage of promyelocyte differentiation. Conventional treatment with Retinoic acid and chemotherapeutics is quite satisfactory. However, there are still patients who relapse or develop resistance to conventional treatment. To propose new possibilities for acute leukemia treatment, we studied the potential of histone deacetylase (HDAC) inhibitor and histone methyl transferase (HMT) inhibitor to enhance conventional therapy in vitro and ex vivo. NB4 and HL60 cell lines were used as an in vitro model; APL patient bone marrow mononuclear cells were used as an ex vivo model. Cell samples were treated with Belinostat (HDAC inhibitor) and 3-Deazaneplanocin A (HMT inhibitor) in combination with conventional treatment (Retinoic acid and Idarubicin). We demonstrated that the combined treatment used in the study had slightly higher effect on cell proliferation inhibition than conventional treatment. Also, enhanced treatment showed stronger effect on induction of apoptosis and on suppression of metabolism. Moreover, the treatment accelerated granulocytic cell differentiation and caused chromatin remodelling (increased H3K14 and H4 acetylation levels). In vitro and ex vivo models showed similar response to the treatment with different combinations of 3-Deazaneplanocin A, Belinostat, Retinoic acid, and Idarubicin. In conclusion, we suggest that 3-Deazaneplanocin A and Belinostat enhanced conventional acute promyelocytic leukemia treatment and could be considered for further investigations for clinical use.

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Growth Inhibition Accompanied by MOB1 Upregulation in Human Acute Lymphoid Leukemia Cells by 3-Deazaneplanocin A

Cited by 7 publications

References 35 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

MOB (Mps one Binder) Proteins in the Hippo Pathway and Cancer

HDAC and HMT Inhibitors in Combination with Conventional Therapy: A Novel Treatment Option for Acute Promyelocytic Leukemia

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