miR-29b restrains cholangiocarcinoma progression by relieving DNMT3B-mediated repression of CDKN2B expression

Cao, Kejiang; Li, Bo; Zhang, Yewei; Song, Hui; Chen, Yigang; Gong, Yongjun; Li, Haiyang; Zuo, Shi

doi:10.18632/aging.202549

Cited by 14 publications

(14 citation statements)

References 34 publications

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“…Mechanistically, we found that genetic DNMT3B depletion blocks UPS cell proliferation by inhibiting DNA synthesis and causing cells to accumulate in G1-phase of the cell cycle. Similar findings have been reported in rhabdomyosarcoma, a pediatric skeletal muscle tumor (Megiorni et al , 2016), as well as in epithelial cancers such as pancreatic, bladder, and cholangiocarcinomas (Cao et al , 2021; Gao et al , 2013; Ying et al , 2020). In normal cells, G1-phase growth arrest is typically induced by p53 stabilization and transcription of its downstream targets (Agarwal et al , 1995).…”

Section: Discussionsupporting

confidence: 83%

Comparative oncology reveals DNMT3B as a molecular vulnerability in soft-tissue sarcoma

Fuller

DeVine

Murazzi

et al. 2021

Preprint

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Undifferentiated pleomorphic sarcoma (UPS), an aggressive subtype of soft-tissue sarcoma (STS), is exceedingly rare in humans and lacks effective, well-tolerated therapies. In contrast, STS are relatively common in canine companion animals; thus, incorporation of veterinary patients into studies of UPS offers an exciting opportunity to develop novel therapeutic strategies for this rare human disease. Genome-wide studies have demonstrated that UPS is characterized by aberrant patterns of DNA methylation. However, the mechanisms and impact of this epigenetic modification on UPS biology and clinical behavior are poorly understood. Leveraging cell lines and tissue specimens derived from human and canine patients, we discovered that the DNA methyltransferase DNMT3B is overexpressed in UPS relative to normal mesenchymal tissues and associated with a poor prognosis. Consistent with these findings, genetic DNMT3B depletion strongly inhibited UPS cell proliferation and tumor progression. However, existing hypomethylating agents, including the clinically approved drug 5-aza-2'-deoxycytidine and the DNMT3B-inhibiting tool compound nanaomycin A, were ineffective in UPS due to cellular uptake and toxicity issues. Thus, further development of DNMT3B-targeting strategies for these patients is critical.

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Section: Discussionsupporting

confidence: 83%

Comparative oncology reveals DNMT3B as a molecular vulnerability in soft-tissue sarcoma

Fuller

DeVine

Murazzi

et al. 2021

Preprint

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“…The negative correlation between miR-29s and DNMTs has been explored in many diseases, such as cholangiocarcinoma ( Cao, et al, 2021 ), osteoarthritis ( Dou, et al, 2020 ), and leukemia ( Qiu, et al, 2018 ). The enforced expression of miR-29s regulated downstream genes mediated by DNMT3B ( Cao, et al, 2021 ; Qiu, et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

miR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes

Yang

et al. 2022

Front. Cell Dev. Biol.

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As a member of the miR-29 family, miR-29b regulates global DNA methylation through target DNA methyltransferases (DNMTs) and acts as both a target and a key effector in DNA methylation. In this study, we found that miR-29b-3p expression was inversely correlated with DNMT expression in the heart tissues of patients with congenital heart disease (CHD), but whether it interacts with DNMTs in cardiomyocytes remains unknown. Further results revealed a feedback loop between miR-29b-3p and DNMTs in cardiomyocytes. Moreover, miR-29b-3p inhibitor relieved the deformity of hypomethylated zebrafish and restored the DNA methylation patterns in cardiomyocytes, resulting in increased proliferation and renormalization of gene expression. These results suggest mutual regulation between miR-29b-3p and DNMTs in cardiomyocytes and support the epigenetic normalization of miRNA-based therapy in cardiomyocytes.

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“…In cells overexpressing miR‐29b, the methylation signature of the promoter of the cell cycle inhibitor gene CDKN2B was reduced. MiR‐29b inhibits the progression of cholangiocarcinoma by releasing the inhibition of CDKN2B expression mediated by DNMT3B 10 . FOXC1 induced CTH promoter DNA hypermethylation through upregulation of DNMT3B to promote proliferation and metastasis in primary hepatocellular carcinoma 11 .…”

Section: Discussionmentioning

confidence: 99%

“…MiR‐29b inhibits the progression of cholangiocarcinoma by releasing the inhibition of CDKN2B expression mediated by DNMT3B. 10 FOXC1 induced CTH promoter DNA hypermethylation through upregulation of DNMT3B to promote proliferation and metastasis in primary hepatocellular carcinoma. 11 We found that the expression level of DNMT1 mRNA of PC9, A549, and HCC827 were higher than that of BEAS‐2B, while the expression level of A549 and HCC827 was lower than the expression levels of A549 and HCC827 were lower than those of BEAS‐2B.…”

Section: Discussionmentioning

confidence: 99%

Low‐level EFCAB1 promoted progress by upregulated DNMT3B and could be as a potential biomarker in lung adenocarcinoma

Xiang

Shi

Huang

et al. 2021

Clinical Laboratory Analysis

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Background Lung adenocarcinoma (LUAD) incidence is on the rise. We found that EFCAB1 (EF‐Hand Calcium Binding Domain 1) was significantly downregulated in LUAD tissues, but the mechanism of EFCAB1 is unknown. Methods One hundred and two LUAD samples and corresponding NT samples were prospectively collected from patients at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, from August 2018 to August 2021.EFCAB1 expression was estimated in LUAD cells and tissues by qPCR. In‐vitro cytology assays were used to detect the role of EFCAB1 in LUAD cells. Results EFCAB1 expression level of LUAD was significantly lower than it's adjacent cancer tissues and that of LUAD with big tumor size (>2 cm) was significantly lower than that of small tumor size (≤2 cm) group. It shown that expression levels of EFCAB1 from A549, HCC827, PC9 were lowly expressed. The cell migration, invasion, colony formation, proliferation ability of EFCAB1 OE A549, PC9 were lower than that of EFCAB1 OE A549, PC9 NC group, while the apoptotic cells percentage of the EFCAB1 OE A549, PC9 group were significantly increased. We found that DNMT1 mRNA expression level of PC9 was higher than that of BEAS‐2B, while these of A549, HCC827 decreased. Compared with BEAS‐2B, DNMT3A mRNA expression level of PC9 increased. DNMT3B mRNA expression level of PC9, HCC827 were higher than these of BEAS‐2B. Conclusion The EFCAB1 mRNA in LUAD patients and cell lines were downregulated; EFCAB1 overexpression inhibited cell proliferation, migration, invasion, while promoted apoptosis. EFCAB1 was expected to become a biomarker of LUAD.

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miR-29b restrains cholangiocarcinoma progression by relieving DNMT3B-mediated repression of CDKN2B expression

Cited by 14 publications

References 34 publications

Comparative oncology reveals DNMT3B as a molecular vulnerability in soft-tissue sarcoma

Comparative oncology reveals DNMT3B as a molecular vulnerability in soft-tissue sarcoma

miR-29b-3p Inhibitor Alleviates Hypomethylation-Related Aberrations Through a Feedback Loop Between miR-29b-3p and DNA Methylation in Cardiomyocytes

Low‐level EFCAB1 promoted progress by upregulated DNMT3B and could be as a potential biomarker in lung adenocarcinoma

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