BRD4 promotes the stemness of gastric cancer cells via attenuating miR-216a-3p-mediated inhibition of Wnt/β-catenin signaling

Hu, Song; Shi, Linseng; Xu, Yixin; Xu, Teng; Fan, Ruizhi; Cao, Meng; Xu, Wei; Song, Jun

doi:10.1016/j.ejphar.2019.03.018

Cited by 41 publications

(34 citation statements)

References 26 publications

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“…He et al, 2015). miR-216a-3p has been recently proposed as a cancer-associated miRNA in several cancer types (Song et al, 2019;Wang, Li, Zhang, Li, & Yu, 2018;Wu et al, 2018). To date, whether miR-216a-3p is dysregulated in cervical cancer and contributes to the progression of cervical cancer remains unexplored.…”

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confidence: 99%

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

Zhao

Yang

2020

Journal Cellular Physiology

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The tumor‐suppressive role of microRNA‐216a‐3p (miR‐216a‐3p) has been evidenced in multiple tumors. Yet, the relevance of miR‐216a‐3p in cervical cancer remains undermined. The current study was designed to determine the expression and potential function of miR‐216a‐3p in cervical cancer. Expression of miR‐216a‐3p was markedly decreased in cervical cancer and functional assays revealed an inhibitory effect of miR‐216a‐3p on the proliferation, colony formation, and invasion of cervical cancer. Actin‐like 6A (ACTL6A) was identified as a target gene of miR‐216a‐3p. Elevated ACTL6A expression was detected in cervical cancer, and ACTL6A inhibition exhibited a tumor‐suppressive effect. ACTL6A inhibition increased yes‐associated protein (YAP) phosphorylation and downregulated YAP‐mediated transcriptional activity. ACTL6A restoration or YAP reactivation partially abrogated the miR‐216a‐3p‐mediated antitumor effect in cervical cancer cells. Taken together, these data demonstrate that miR‐216a‐3p acts as a potential tumor‐suppressive miRNA in cervical cancer, which exerts its function through inhibition of YAP signaling via targeting ACTL6A.

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confidence: 99%

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

Zhao

Yang

2020

Journal Cellular Physiology

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“…Combined bioinformatics assays, miR‐142‐5p was identified as the target of BRD4 by ChIP and luciferase reporter analysis and BRD4 increases the methylation level of miR‐142‐5p promoter. Notably, a recent work shows that BRD4 could directly bind to miR‐216a promoter and thus increases its methylation level, which is responsible for BRD4‐mediated effects on gastric cancer stemness . Since one transcriptional factor could have many targets, we wonder whether the BRD4/miR‐216a axis exists in glioma and the BRD4/miR‐142‐5p axis exists in other tumors, this should be explored in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Since one transcriptional factor could have many targets, we wonder whether the BRD4/miR‐216a axis exists in glioma and the BRD4/miR‐142‐5p axis exists in other tumors, this should be explored in the future. Furthermore, it must be noted that the mechanisms by which the methylation level of miR‐142‐5p promoter is regulated are still unclear, we speculate that BRD4 might interact with the DNA methyltransferase DNMT1 because the BRD4‐DNMT1 interaction has been proved in gastric cancer …”

Section: Discussionmentioning

confidence: 99%

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BRD4 promotes glioma cell stemness via enhancing miR‐142‐5p‐mediated activation of Wnt/β‐catenin signaling

Wang

et al. 2019

Environmental Toxicology

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The bromodomain protein BRD4 exerts carcinogenic effects in many cancers. However, its roles in glioma occurrence are still confused. Here, it is found that BRD4 expression is increased in glioma tissues and negatively correlated with the overall survival of glioma patients. We construct cellular experiments indicating that BRD4 promotes glioma cell stemness by analyzing ALDH1 activity, master stemness regulator expression, and sphere formation ability. Mechanistically, BRD4 knockdown triggers a switch of miR-142-5p promoter methylation, which targets Wnt3a and thus further inactivates Wnt/β-catenin signaling. Importantly, inhibition of miR-142-5p or reactivation of Wnt/β-catenin signaling rescues the inhibition of BRD4 knockdown on glioma cell stemness. As a result, these results not only indicate an unforeseen connection between BRD4, miR-142-5p, and Wnt/β-catenin signaling, but also reveal a promising epigenetic-based therapeutic strategy that might be explored for glioma patients. K E Y W O R D SBRD4, glioma, miR-142-5p, Stemness, Wnt/β-catenin

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“…In Tao et al, overexpression of miR-216a led to the activation of E-cadherin and inhibited EMT in in vitro experiments. The decreased level of miR-216a expression correlated with metastasis to the lymph nodes in patients with GC [42,43]. At the same time, miR-216a is an inducer of the NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 88%

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

et al. 2020

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Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

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BRD4 promotes the stemness of gastric cancer cells via attenuating miR-216a-3p-mediated inhibition of Wnt/β-catenin signaling

Cited by 41 publications

References 26 publications

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

BRD4 promotes glioma cell stemness via enhancing miR‐142‐5p‐mediated activation of Wnt/β‐catenin signaling

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

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