miR-30 disrupts senescence and promotes cancer by targeting both p16INK4A and DNA damage pathways

Su, Weijun; Hong, Lian; Xu, Xin; Huang, Shan; Herpai, Denise; Liu, Lisheng; Xu, Yingxi; Truong, Lan N.; Hu, Wen-Yuan; Wu, Xiaohua; Xiao, Changchun; Zhang, Wei; Han, Jiahuai; Debinski, Waldemar; Xiang, Rong; Sun, Peiqing

doi:10.1038/s41388-018-0358-1

Cited by 44 publications

(37 citation statements)

References 49 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As can be seen, among them, most of the pathways in one way or another are associated with tumor suppression, as well as regulation of gene expression due to miRNAs. This is mainly about genes: CCND1, CCND2, CDK4, CDKN1A, SESN2, SESN3, TNFRSF10B, TNRC6A/B/C, BTG2, TP53, PPP2CA , most of them are tumor suppressors [ 91 – 94 ]. Of course, the list of enriched pathways was not limited to those associated with tumor suppression.…”

Section: Resultsmentioning

confidence: 99%

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

et al. 2020

View full text Add to dashboard Cite

Background Prostate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies. Methods High-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 – 20 samples; N0 – 24 samples). Results We found at least 18 microRNAs with differential expression between N0 and N1 sample groups: miR-182-5p, miR-183-5p, miR-96-5p, miR-25-3p, miR-93-5p, miR-7-5p, miR-615-3p, miR-10b, miR-1248 (N1-miRs; elevated expression in N1 cohort; p < 0.05); miR-1271-5p, miR-184, miR-222-3p, miR-221-5p, miR-221-3p, miR-455-3p, miR-143-5p, miR-181c-3p and miR-455-5p (N0-miRs; elevated expression in N0; p < 0.05). The expression levels of N1-miRs were highly correlated between each other (the same is applied for N0-miRs) and the expression levels of N0-miRs and N1-miRs were anti-correlated. The tumor samples can be divided into two groups depending on the expression ratio between N0-miRs and N1-miRs. Conclusions We found the miRNA expression signature associated with lymphatic dissemination, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.

show abstract

Section: Resultsmentioning

confidence: 99%

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Since PTEN initiates DNA damage responses and miR-30c has been shown to disrupt DNA damage responses, we investigated the epigenetic regulation of PTEN [ 26 , 38 ]. miR-30c is involved in regulating cell cycle transition, proliferation, and lipid metabolism.…”

Section: Resultsmentioning

confidence: 99%

Fumonisin B1 Epigenetically Regulates PTEN Expression and Modulates DNA Damage Checkpoint Regulation in HepG2 Liver Cells

Arumugam

Ghazi

Chuturgoon

2020

Toxins

View full text Add to dashboard Cite

Fumonisin B1 (FB1), a Fusarium-produced mycotoxin, is found in various foods and feeds. It is a well-known liver carcinogen in experimental animals; however, its role in genotoxicity is controversial. The current study investigated FB1-triggered changes in the epigenetic regulation of PTEN and determined its effect on DNA damage checkpoint regulation in human liver hepatoma G2 (HepG2) cells. Following treatment with FB1 (IC50: 200 µM; 24 h), the expression of miR-30c, KDM5B, PTEN, H3K4me3, PI3K, AKT, p-ser473-AKT, CHK1, and p-ser280-CHK1 was measured using qPCR and/or Western blot. H3K4me3 enrichment at the PTEN promoter region was assayed via a ChIP assay and DNA damage was determined using an ELISA. FB1 induced oxidative DNA damage. Total KDM5B expression was reduced, which subsequently increased the total H3K4me3 and the enrichment of H3K4me3 at PTEN promoters. Increased H3K4me3 induced an increase in PTEN transcript levels. However, miR-30c inhibited PTEN translation. Thus, PI3K/AKT signaling was activated, inhibiting CHK1 activity via phosphorylation of its serine 280 residue preventing the repair of damaged DNA. In conclusion, FB1 epigenetically modulates the PTEN/PI3K/AKT signaling cascade, preventing DNA damage checkpoint regulation, and induces significant DNA damage.

show abstract

“…Also, the loss of KDM6B enhances the aggressiveness of PDAC cells by inhibiting the expression of C/EBP α [ 57 ]. TNRC6A, an essential mRNA-binding protein in miRISC, is inducing the DDRNA expression and functionality; and miR-30 promotes cancer by suppressing TNRC6A [ 58 ]. Shukla et al discussed DNM1 may participate in driving long-term radiation toxicity in the brain [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

Zhu

Zhou

Zhu

et al. 2021

Mediators of Inflammation

View full text Add to dashboard Cite

Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Inflammation-associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein-protein interaction (PPI) networks of inflammation-associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan-Meier plotter databases, respectively. The circRNA_102049/miR-455-3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR-455-3p were explored by RT-PCR, western blot, and dual-luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR-455-3p and partially reversed the effect of miR-455-3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

show abstract

miR-30 disrupts senescence and promotes cancer by targeting both p16INK4A and DNA damage pathways

Cited by 44 publications

References 49 publications

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

miRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer

Fumonisin B1 Epigenetically Regulates PTEN Expression and Modulates DNA Damage Checkpoint Regulation in HepG2 Liver Cells

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

Contact Info

Product

Resources

About