KDM4B promotes gastric cancer metastasis by regulating miR‐125b‐mediated activation of Wnt signaling

Jing, Jia-Chen; Feng, Zhen; Chen, Zhonghua; Ji, Bei-Na; Jiang, Hong; Tang, Nan; Yü, Jin; Wang, Shaoying

doi:10.1002/jcb.28065

Cited by 21 publications

(20 citation statements)

References 40 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During recent years, researchers have explored the potential mechanism by which miRNA-125b (precursor of miRNA-125b-5p) is involved in gastric cancer. One other previous research showed that miR-125b was as an intermediary between KDM4B (a histone-modifying enzyme) and Wnt signaling [ 18 ]. Another demonstrated that miR-125b targeted the PPP1CA-Rb signal pathway to enhance the migration and invasion of gastric carcinoma cells [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Use of a Four-miRNA Panel as a Biomarker for the Diagnosis of Stomach Adenocarcinoma

Chen

Peng

et al. 2020

Disease Markers

View full text Add to dashboard Cite

Background. MicroRNAs (miRNAs) have been applied to cancer diagnosis taking into account their role in tumorigenesis. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis. Methods. A total of 246 participants (130 STAD patients and 116 healthy controls (HCs)) were enrolled in this 3-phase study. Five STAD pools and 3 HC pools (with 4 participants in each pool) were used for the screening of the 28 miRNAs using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The training phase (30 STAD patients vs. 24 HCs) and validation phase (80 STAD patients vs. 80 HCs) were used to further verify the identity of these miRNAs. Kaplan–Meier survival analysis and bioinformatics analysis were also used. Results. The expression levels of miR-125b-5p and miR-196a-5p were upregulated in STAD serum, compared with the HCs, while miR-1-3p and miR-149-5p showed the opposite result. A four-serum miRNA panel was constructed, and the area under the receiver operating characteristic curve (AUC) was found to be 0.892 (95% CI: 0.834 to 0.936, sensitivity = 86.25 % , specificity = 78.75 % ). Only miR-125b-5p expression showed a significant difference between STAD patients and NCs in the survival analysis. The neurotrophin signaling pathway was associated with 4 miRNAs identified in STAD patients. Conclusion. The four-serum miRNA panel has great potential to be used as a noninvasive biomarker for STAD diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Use of a Four-miRNA Panel as a Biomarker for the Diagnosis of Stomach Adenocarcinoma

Chen

Peng

et al. 2020

Disease Markers

View full text Add to dashboard Cite

show abstract

“…It has been previously reported that the Wnt/β-catenin signaling pathway is of great importance in regulating tumor cell growth and metastasis (27,28), and inactivation of Wnt/β-catenin signaling suppresses the growth and progression of numerous cancers, including NSCLC (29). Increasing evidence has revealed that active Wnt/β-catenin signaling can lead to T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy in melanoma (16).…”

Section: Discussionmentioning

confidence: 99%

IL‑21/IL‑21R inhibit tumor growth and invasion in non‑small cell lung cancer cells via suppressing Wnt/β‑catenin signaling and PD‑L1 expression

et al. 2019

View full text Add to dashboard Cite

Lung cancer is considered to be one of the world's deadliest diseases, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. The present study aimed to investigate the role and underlying mechanisms of interleukin-21 (IL-21), and its receptor IL-21R, in NSCLC. Lung tissues and blood samples of NSCLC were used to measure IL-21, IL-21R and programmed death 1 ligand 1 (PD-L1) expression using ELISA, western blot and immunohistochemistry analyses. Following treatment with different doses of IL-21, the proliferation, invasion and migration of human NSCLC cell line A549 was evaluated using a cell counting kit-8, colony formation, Transwell and scratch wound healing assays, respectively. Additionally, IL-21R and PD-L1 expression in A549 cells was detected using western blot analysis and immunofluorescence. IL-21R silencing was subsequently used to investigate its effects in cell proliferation, invasion and migration. PD-L1, IL-1β and tumor necrosis factor α (TNF-α) expression were measured. Finally, Wnt/β-catenin signaling expression was evaluated using western blot analysis following treatment with IL-21. Cells were then treated with lithium chloride (LiCl), which is an agonist of Wnt/β-catenin signaling, and the levels of PD-L1, IL-1β and TNF-α were detected. The results revealed that IL-21 and IL-21R expression in the lung tissues and blood samples of patients with NSCLC were decreased, while PD-L1 expression was increased, compared with normal tissues or healthy controls. Treatment of A549 cells with IL-21 upregulated IL-21R expression, downregulated PD-L1 and inhibited cell growth and metastasis in a dose-dependent manner. Following IL-21R silencing, the effects of IL-21 treatment were reversed, suggesting that IL-21 acted on A549 cells through binding to IL-21R. In addition, the results demonstrated that IL-21 treatment reduced the expression levels of proteins associated with the Wnt/β-catenin signaling, whereas activation of Wnt/β-catenin signaling with the LiCl agonist upregulated PD-L1, IL-1β and TNF-α expression. In conclusion, the IL-21/IL-21R axis reduced the growth and invasion of NSCLC cells via inhibiting Wnt/β-catenin signaling and PD-L1 expression. The present results may provide a novel molecular target for NSCLC diagnosis and therapy.

show abstract

“…KDM4B binds to the promoter of β‐catenin target genes and increase its transcription via H3K9 demethylation. KDM4B also upregulates miR‐125b expression and activates the Wnt signaling pathway . After Helicobacter pylori infection, KDM4B induced by the β‐catenin pathway along with nuclear factor‐κB (NF‐κB) binds to the cyclooxygenase‐2 (COX‐2) promoter to COX2 transcription .…”

Section: Altered Expression and Functions Of Kdm4s In Cancermentioning

confidence: 99%

“…80,100 KDM4B knockdown markedly suppresses tumor proliferation and xenograft tumor growth in vivo, 80 while KDM4B inhibition by targeted siRNA or miR-491-5p reduces the migration and invasion of gastric cancer cells in vitro 100 and metastasis in vivo. 101,102 In addition, inhibition of KDM4B prevents the EMT of gastric cancer cells, whereas ectopic overexpression of KDM4B induces EMT. The expression level of KDM4B is also positively correlated with TNM stage, tumor differentiation status, tumor size, tumor invasion, lymph node metastasis, and distant metastasis in gastric cancer patients KDM4B expression is induced via the β-catenin signaling pathway and contributes to the regulation of other downstream target genes through physical association with β-catenin.…”

Section: Gastric Cancermentioning

confidence: 99%

“…KDM4B also upregulates miR-125b expression and activates the Wnt signaling pathway. 102 After Helicobacter pylori infection, KDM4B induced by the β-catenin pathway along with nuclear factor-κB (NF-κB) binds to the cyclooxygenase-2 (COX-2) promoter to COX2 transcription. 103 Expression levels of KDM4B and COX-2 gradually increase in human gastric tissues during progression from infection-related gastritis to gastric cancer.…”

Section: Gastric Cancermentioning

confidence: 99%

See 1 more Smart Citation

Advances in histone demethylase KDM4 as cancer therapeutic targets

et al. 2020

View full text Add to dashboard Cite

The KDM4 subfamily H3K9 histone demethylases are epigenetic regulators that control chromatin structure and gene expression by demethylating histone H3K9, H3K36, and H1.4K26. The KDM4 subfamily mainly consists of four proteins (KDM4A‐D), all harboring the Jumonji C domain (JmjC) but with differential substrate specificities. KDM4A‐C proteins also possess the double PHD and Tudor domains, whereas KDM4D lacks these domains. KDM4 proteins are overexpressed or deregulated in multiple cancers, cardiovascular diseases, and mental retardation and are thus potential therapeutic targets. Despite extensive efforts, however, there are very few KDM4‐selective inhibitors. Defining the exact physiological and oncogenic functions of KDM4 demethylase will provide the foundation for the discovery of novel potent inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM4s and the interplay between KDM4‐mediated epigenetic and metabolic pathways in cancer. We also review currently available KDM4 inhibitors and discuss their potential as therapeutic agents for cancer treatment.

show abstract

KDM4B promotes gastric cancer metastasis by regulating miR‐125b‐mediated activation of Wnt signaling

Cited by 21 publications

References 40 publications

Use of a Four-miRNA Panel as a Biomarker for the Diagnosis of Stomach Adenocarcinoma

Use of a Four-miRNA Panel as a Biomarker for the Diagnosis of Stomach Adenocarcinoma

IL‑21/IL‑21R inhibit tumor growth and invasion in non‑small cell lung cancer cells via suppressing Wnt/β‑catenin signaling and PD‑L1 expression

Advances in histone demethylase KDM4 as cancer therapeutic targets

Contact Info

Product

Resources

About