A novel regulatory circuit of miR‑152 and DNMT1 in human bladder cancer

Zhang, Haiqing; Qi, Defeng; Li, Jinhui; Peng, Tao; Liu, Yang; Yuan, Jun; Zhang, Yuying; Hu, Yuan; Su, Jialin; Que, Biao; Li, Mengxi; Zhou, Guoren; Chen, Yuxin; Zhang, Wenjuan; Ji, Weidong

doi:10.3892/or.2018.6553

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…However, differential expression according to tumour grade was observed. Finally, recent findings support a possible promising role of DNMT1 as early biomarker for UCB (32).…”

Section: Discussionmentioning

confidence: 55%

Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria

et al. 2019

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The aim of the present study was to identify and test a urine marker panel of genes involved in DNA methylation and histone modification for the detection of urothelial carcinoma of the bladder (UCB). RNA samples obtained from the voided urine of 227 patients with asymptomatic microscopic haematuria (AMH) were analysed. Gene array analysis was performed on 18 randomly selected cDNA samples, which revealed that histone deacetylase 9 (HDAC9), HDAC3, tRNA (cytosine-5-)-methyltransferase1 and DNA methyltransferase 1 were differentially expressed between patients with UCB and control subjects. Subsequently, reverse transcription-quantitative polymerase chain reaction analysis was employed to test the performance of the identified four-gene panel on the remaining 209 cDNA samples. In this targeted discovery cohort, all four genes were significantly associated with UCB on univariable analyses [each odds ratio (OR) >2, P<0.05], but only HDAC3 was significant following multivariable analysis (OR=2.8, P=0.011). The addition of HDAC3 to a base risk factor model improved its accuracy by 1.4%. These data suggest that urinary HDAC3 is associated with the presence of UCB in patients with AMH; however, HDAC3

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“…However, differential expression according to tumour grade was observed. Finally, recent findings support a possible promising role of DNMT1 as early biomarker for UCB (32).…”

Section: Discussionmentioning

confidence: 55%

Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria

et al. 2019

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“…miRNA-148b suppressed cell cycle progression and facilitated cell apoptosis by regulating DNMT1 in cervical cancer [26] and endometrial cancer [27] in a caspase-3 dependent manner. miR-152 inhibited the proliferation, migration, or invasion by targeting the DNMT1 3′UTR directly in hepatitis B virus-related hepatocellular carcinoma [28], ovarian cancer [29], glioma [30], nasopharyngeal cancer [31] and bladder cancer cells [32]. All these findings indicate that DNMTs are downstream targets of miR-148/-152 family members in various types of cancer.…”

Section: Discussionmentioning

confidence: 88%

Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells

Lee

Kim

et al. 2023

Clin Epigenet

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Background To understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells. Methods Expression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq. Results Metformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3′UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3′UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09—6.47; P = 0.04) but not with recurrence-free survival. Conclusions The present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells.

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“…For experiments using FFPE tissue, the expression of miRNA genes reportedly altered in UC, including miR-181a, 32 miR-143, 2,20,54 miR-152, 27,60,61 and miR-214, 59 were utilized in the qPCR procedure, in addition to reference gene miR-1842. 54 For miRNA stability experiments in urine in different storage conditions, we measured miRNAs that were expected to be expressed consistently within the urothelium: namely miR-30c 56 and miR-1842.…”

Section: Methodsmentioning

confidence: 99%

Canine urothelial carcinoma: a pilot study of microRNA detection in formalin-fixed, paraffin-embedded tissue samples and in normal urine

Varvil,

Clark,

Bailey

et al. 2023

J VET Diagn Invest

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We assessed the effects of fixation time in formalin and inclusion of surrounding tissue on microRNA (miRNA) cycle quantification (Cq) values in formalin-fixed, paraffin-embedded (FFPE) urothelial carcinoma (UC) tissue ( n = 3), and the effect of conditions on miRNAs in urine from 1 healthy dog. MiRNAs were extracted using commercial kits and quantified using miRNA-specific fluorometry in normal bladder tissue scrolls, UC tissue cores, and bladder muscularis tissue cores from 4 FFPE bladder sections (3 UCs, 1 normal), plus 1 UC stored in formalin for 1, 8, 15, and 22 d before paraffin-embedding. Urine was collected from a healthy dog on 4 occasions; 1-mL aliquots were stored at 20, 4, −20, and −80°C for 4, 8, 24, and 48 h, and 1 and 2 wk. For both FFPE tissue and urine, we used reverse-transcription quantitative real-time PCR (RT-qPCR) to quantify miR-143, miR-152, miR-181a, miR-214, miR-1842, and RNU6B in each tissue or sample, using miR-39 as an exogenous control gene. The Cq values were compared with ANOVA and t-tests. The time of tissue-fixation in formalin did not alter miRNA Cq values; inclusion of the muscularis layer resulted in a statistically different miRNA Cq profile for miR-152, miR-181a, and RNU6B in bladder tissue. MiRNAs in acellular urine were stable for up to 2 wk regardless of the storage temperature. Our findings support using stored FFPE and urine samples for miRNA detection; we recommend measuring miRNA only in the tissue of interest in FFPE sections.

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A novel regulatory circuit of miR‑152 and DNMT1 in human bladder cancer

Cited by 9 publications

References 46 publications

Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria

Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria

Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells

Canine urothelial carcinoma: a pilot study of microRNA detection in formalin-fixed, paraffin-embedded tissue samples and in normal urine

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