DNMT1 activates the canonical Wnt signaling in rheumatoid arthritis model rats via a crucial functional crosstalk between miR-152 and the DNMT1, MeCP2

Miao, Chenggui; Qin, Dan; Du, Cheng; Hua, Yingqi; Wei-jing, Shi; Xiong, Youyi; Zhang, Xiaolin; Yu, Hao; Dou, Jing; Ma, Shi-Tang; Qin, Meisong; Liu, Han-zhen; Fang, Yan-xi; Zhou, Guoliang; Chen, Jianzhong; He, Xu; Huang, Cheng; Huang, Yan; Zhang, Bing; Song, Tong-wen; Li, Jun

doi:10.1016/j.intimp.2015.06.013

Cited by 28 publications

(19 citation statements)

References 39 publications

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“…Consistent with this study, our results demonstrated the downregulation of miR-152 expression in BC as well as the hypermethylation at the promoter region of miR-152. Notably, we identified that the DNMT1 bound to the miR-152 CpG island promoter was markedly decreased in T24 cells transfected with miR-152 mimics, which was similar to a previous study revealing that the overexpression of miR-152 decreased DNMT1 and MeCP2 binding to the CpG island promoter of miR-152 in an FLS model (36). In addition, it was revealed that miR-152 could act as a tumor suppressor by targeting TGF, and inhibit prostate cancer cell migration and invasion (37).…”

Section: Discussionsupporting

confidence: 90%

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

Zhang

et al. 2018

Oncol Rep

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Downregulation of microRNA‑152 (miR‑152) has been observed in various types of human malignancies, including Bladder cancer (BC). However, the role of miR‑152 in the development and progression of BC is still unclear. In our previous study, we identified a functional crosstalk between miR‑152 and DNA methyltransferase 1 (DNMT1) involved in Nis‑induced malignant transformation. In the present study, we found that the expression of miR‑152 was specifically downregulated in BC cells and tissues via the DNA hypermethylation of the miR‑152 promoter. The overexpression of miR‑152 in BC cells resulted in a reduction of DNMT1, whereas the inhibition of the expression of miR‑152 induced an elevated level of DNMT1. Further studies revealed that miR‑152 directly downregulated the expression of DNMT1 by targeting the 3'‑UTR of its transcript in BC cells. In addition, ectopic expression of miR‑152 in BC cells significantly inhibited cell proliferation, whereas the inhibition of miR‑152 expression led to increased cell proliferation. These findings indicated a novel regulatory circuit of miR‑152/DNMT1 in BC, and more importantly, the combination of miR‑152 and DNMT1 may function as promising therapeutic modalities and early biomarkers for BC.

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Section: Discussionsupporting

confidence: 90%

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

Zhang

et al. 2018

Oncol Rep

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“…miR-152, a member of the miR-148/152 family, has been reported to be involved in a series of cell activities, including cell proliferation, apoptosis, cell cycle arrest, invasion and angiogenesis (10)(11)(12)(13)(14)(15)(16)(17)(18). Accumulating evidence has suggested that miR-152 has crucial roles in autoimmune disorders, chronic inflammatory diseases and multiple types of cancer (30,31).…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence has suggested that miR-152 has crucial roles in autoimmune disorders, chronic inflammatory diseases and multiple types of cancer (30,31). miR-152 has been reported to be downregulated in an arthritic rat model, and to decrease FLS proliferation by inhibiting Wnt pathway activation (17,18). However, the functional significance and molecular mechanisms underlying the role of miR-152 in RA remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, miR-152 inhibits the interferon-β-mediated upregulation of major histocompatibility complex class II and the dendritic cell-initiated antigen-specific T cell proliferation by targeting Calcium/calmodulin-dependent protein kinase type II α chain (caMKIIα) (16), suggesting that miR-152 is involved in regulating the immune response. As far as RA is concerned, miR-152 has been demonstrated to be downregulated in an arthritic rat model (17,18), and to decrease FLS proliferation by inhibiting Wnt pathway activation (18). However, the functional significance and molecular mechanisms underlying the role of miR-152 in human RA remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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miR‑152 inhibits rheumatoid arthritis synovial fibroblast proliferation and induces apoptosis by targeting ADAM10

Guo

Fei

et al. 2018

Int J Mol Med

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miR‑152 has been reported to be downregulated in rheumatoid arthritis (RA). However, the functional significance and molecular mechanisms underlying the role of miR‑152 in RA remain largely unknown. The present study aimed to explore the functional role and the underlying mechanisms of miR‑152 in RA. The expression of miR‑152 in serum, synovial tissues, and fibroblast‑like synoviocytes (FLS) from patients with RA and healthy controls was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Cell proliferation, cell cycle phase distribution and apoptosis of FLS were measured by Cell Counting Kit‑8 and flow cytometry assays. The effects of miR‑152 on the production of pro‑inflammatory cytokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6 and IL‑8, were examined by ELISA. The target gene of miR‑152 was discovered by miRNA‑target prediction bioinformatics analysis, and confirmed by dual‑luciferase reporter assay, RT‑qPCR and western blotting. Spearman's correlation analysis was performed to assess the relationship between miR‑152 expression and a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10). The results demonstrated that miR‑152 expression levels were significantly decreased in RA serum, synovial tissues and RA‑FLS compared with healthy controls. Overexpression of miR‑152 significantly inhibited cell proliferation, promoted cell apoptosis, and decreased TNF‑α, IL‑1β, IL‑6 and IL‑8 production in RA‑FLS cells. Additionally, ADAM10 was demonstrated to be a target of miR‑152, and expression of the two genes was significantly negatively correlated. Of note, restoration of ADAM10 expression partially reversed the effects of miR‑152 on cell proliferation and apoptosis in RA‑FLS. Thus, miR‑152 may serve as a potential target for therapeutic intervention in RA.

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“…Consistent with this study, we treated the GC cells with 5-Aza, a DNA methyltransferase inhibitor, and found that the expression of miR-338-3p and pre-miR-338 was significantly upregulated (Figure 2A). Studies have found that the CpG island promoters of some miRNAs were inactive when MECP2 occupied their CpG islands [15, 42]. We found that the expression of both miR-338-3p, pre-miR-338 and miR-338-5p was regulated by MECP2 (Figure 2, Figure 3A and 3B), and that the method of MECP2 binding on the verified CpG island of miR-338 promoter was identified by chromatin immunoprecipitation(CHIP)(Figure 2G).…”

Section: Discussionmentioning

confidence: 99%

MECP2 promotes the growth of gastric cancer cells by suppressing miR-338-mediated antiproliferative effect

Tong

Zhao

et al. 2016

Oncotarget

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The methyl-CpG-binding protein 2 (MECP2), a transcriptional suppressor, is involved in gene regulation by binding to methylated promoters. We found that MECP2 is overexpressed in gastric cancer (GC), and that Mecp2 knockdown affects the growth of GC cells both in vitro and in vivo. MECP2 can directly bind to the methylated-CpG island of miR-338 promoter and suppress the expression of two mature microRNAs, namely, miR-338-3p and miR-338-5p. Furthermore, miR-338-5p can suppress GC cell growth by targeting BMI1 (B lymphoma Mo-MLV insertion region 1 homolog). We additionally found that decreased miR-338-5p expression in GC tissues, relative to normal tissues, was significantly negatively correlated with increased BMI1 expression. Silencing MECP2 can indirectly lead to reduced expression of P-REX2, which has been identified as the miR-338-3p target, as well as BMI1 and increasing expression of P16 or P21 both in vitro and in vivo. Altogether, our results indicate that MECP2 promote the proliferation of GC cells via miR-338 (miR-338-3p and miR-338-5p)-mediated antitumor and gene regulatory effect.

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DNMT1 activates the canonical Wnt signaling in rheumatoid arthritis model rats via a crucial functional crosstalk between miR-152 and the DNMT1, MeCP2

Cited by 28 publications

References 39 publications

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

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

miR‑152 inhibits rheumatoid arthritis synovial fibroblast proliferation and induces apoptosis by targeting ADAM10

MECP2 promotes the growth of gastric cancer cells by suppressing miR-338-mediated antiproliferative effect

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