microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

Liu, Beibei; Sun, Wei; Gao, Wuyue; Li, Liqiang; Cao, Zhenxue; Yang, Xiaohuai; Liu, Jianmin; Guo, Yuanyuan

doi:10.1186/s12885-020-07523-8

Cited by 14 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lastly, we have not attempted to identify the source of EVcontained miR-451a and miR-486-5p in urine. Both miRNAs are known to be secreted by BC cells [51,58] but are also expressed by other cells, including erythrocytes [59].…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors

Strømme

Heck

Brede

et al. 2021

CIMB

View full text Add to dashboard Cite

Bladder cancer (BC) is currently diagnosed and monitored by cystoscopy, a costly and invasive procedure. Potential biomarkers in urine, blood, and, more recently, extracellular vesicles (EVs), have been explored as non-invasive alternatives for diagnosis and surveillance of BC. EVs are nanovesicles secreted by most cell types containing diverse molecular cargo, including different types of small RNAs, such as microRNA (miRNA). In this study, we performed next-generation sequencing of EV-contained miRNA isolated from urine and serum of 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. MiRNA sequencing was also performed on serum supernatant samples for T1 patients. To identify potential BC-specific biomarkers, expression levels of miRNA in presurgery samples were compared to those at postsurgery check-ups, and to NCPs. Results showed that two miRNAs, urinary EV-contained miR-451a and miR-486-5p, were significantly upregulated in presurgery samples from T1 patients compared to postsurgery check-up samples. This was confirmed in a replica EV/RNA isolation and sequencing run of 10 T1 patients from the primary run; however, analyses revealed no differential expression of miRNAs in serum EVs, serum supernatant, or when comparing BC patients to NCPs. This is the first study to investigate EV-containing miRNA sequencing in pre- and postsurgery BC patient samples and our findings suggest that urinary EV-contained miR-451a and miR-486-5p may be potential biomarkers for recurrence-free survival of BC patients with stage T1 disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors

Strømme

Heck

Brede

et al. 2021

CIMB

View full text Add to dashboard Cite

show abstract

“…Prema Subbarayal et al have suggested that EPHA2 interacts with the p85 subunit of PI3K to activate the PI3K-AKT signaling pathway [ 35 ]. In bladder cancer, Beibei Liu has proved that EPHA2 can promote the growth and metastasis of cancer cells by activating the PI3K/AKT signaling pathway [ 36 ]. The results above remind us of the relationship between EPHA2 and signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

MFSD4A inhibits the malignant progression of nasopharyngeal carcinoma by targeting EPHA2

et al. 2022

View full text Add to dashboard Cite

DNA Methylation can lead to abnormal gene expression. In the present study, we investigated whether the expression of methylated MFSD4A (major facilitator superfamily domain containing 4 A) was downregulated in nasopharyngeal carcinoma (NPC) and whether it is associated with malignant progression and poor prognosis of NPC. Bioinformatic analysis, bisulfite pyrosequencing, quantitative real-time reverse transcription PCR, and western blotting assays were performed to explore the relationship between hypermethylation of MFSD4A and its expression in NPC. The role of MFSD4A in NPC was verified by Cell Cycle Kit 8, transwell assays and flow cytometry in vitro and by animal experiments in vivo. Mass spectrometry, co-immunoprecipitation, and immunofluorescence assays were applied to explore the mechanism by which MFSD4A inhibits NPC. The prognostic significance of MFSD4A or EPHA2 was investigated by immunohistochemical analysis of clinical specimens. Hypermethylation of the promoter region of MFSD4A led to decreased expression of MFSD4A. When MFSD4A expression was upregulated or downregulated, the proliferation, apoptosis, migration, and invasion abilities of NPC cells were altered accordingly. Mechanistically, MFSD4A could specifically bind to and degrade EPH receptor A2 (EPHA2) by recruiting ring finger protein 149 (RNF149), which led to alterations in the EPHA2-mediated PI3K-AKT-ERK1/2 pathway and epithelial-mesenchymal transition (EMT), thereby affecting NPC progression. Clinically, high MFSD4A expression or low-EPHA2 expression was associated with better prognosis for patients with NPC. In all, reduced MFSD4A expression in NPC is caused by promoter hypermethylation. MFSD4A or EPHA2 expression is associated with the malignant biological behavior and prognosis of NPC. MFSD4A is a promising potential therapeutic target for NPC.

show abstract

“…Silencing of MCL1 promoted senescence and apoptosis in glioma cells by impairing the PI3K/AKT signaling pathway [ 33 ]. Moreover, miR-451a promoter methylation regulated by DNMT3B expedited the progression of bladder cancer via the PI3K/AKT axis [ 34 ]. All these findings were line with our observation that DNMT3B/miR-34a/MCL1 axis governs the OA progression via the PI3K/AKT signaling pathway ( Figure 7a , b).…”

Section: Discussionmentioning

confidence: 99%

DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis

Xiong

Zhao

Xu³

2021

Bioengineered

View full text Add to dashboard Cite

Osteoarthritis (OA) is characterized by destruction of articular cartilage with an imbalance between synthesis and degradation of extracellular matrix (ECM). In the current study, we explored the role of microRNA-34a (miR-34a) and the behind epigenetic mechanism in the degradation of ECM in OA. Using miRNA-based microarray analysis, we found that miR-34a was overexpressed in cartilage tissues of OA patients relative to patients with acute traumatic amputations. Moreover, its expression was positively correlated with the ECM degradation and inflammation. Mechanistically, miR-34a targeted MCL1, and possible target genes of miR-34a were enriched in the PI3K/AKT pathway. Furthermore, DNMT3B inhibited miR-34a by promoting miR-34a methylation. Functional experiments using CCK-8, flow cytometry, Safranin O staining, RT-qPCR, ELISA, Western blot, and HE staining revealed that miR-34a inhibitor suppressed ECM degradation and inflammatory response of chondrocytes and cartilage tissues. By contrast, downregulation of DNMT3B and MCL1 reversed the repressive effects of miR-34a inhibitor in vitro and in vivo . Altogether, our findings establish that silencing of miR-34a by DNMT3B could effectively reduce chondrocyte ECM degradation and inflammatory response in mice by targeting MCL1 and mediating the downstream PI3K/AKT pathway. This present study revealed that miR-34a knockdown might develop a novel intervention for OA treatment.

show abstract

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

Cited by 14 publications

References 31 publications

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors

Differentially Expressed Extracellular Vesicle-Contained microRNAs before and after Transurethral Resection of Bladder Tumors

MFSD4A inhibits the malignant progression of nasopharyngeal carcinoma by targeting EPHA2

DNA methyltransferase 3 beta mediates the methylation of the microRNA-34a promoter and enhances chondrocyte viability in osteoarthritis

Contact Info

Product

Resources

About