miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Mo, Li; Guo, Qian; Cai, Hao; Wang, Haiyang; Ma, Zhiming; Zhang, Xuan

doi:10.1002/jcp.29224

Cited by 40 publications

(29 citation statements)

References 42 publications

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“…Consistent with the above findings, we also observed that miR-218 was upregulated in DKD and could reduce cell viability in HGtreated renal tubule cells, which indicated that depletion of miR-218 may protect cells from injury during the development of DKD. However, Li et al, using a rat streptozotocin-induced model of DKD and in vitro HGstimulated mouse podocytes, demonstrated that miR-218 was markedly downregulated in both model systems relative to appropriate controls [19]. We hypothesized that many factors, such as different inducers, and animal or human cells, contributed to this phenomenon.…”

Section: Discussionmentioning

confidence: 88%

“…The mechanism of action of miRNA is mediated by binding target mRNA to inhibit mRNA translation or degrade miRNAbound mRNA, thus inhibiting protein synthesis [15]. By a literature review, it has also revealed that numerous miRNAs are involved in the inflammation of DKD, including miR-218 [16][17][18][19]. It is noted that overexpression of miR-218 can reduce renal injury in a streptozotocin-induced rat model of DKD and can inhibit inflammatory response in the high glucose (HG) induced mouse podocytes by targeting mRNA encoding IKK-b [20].…”

Section: Introductionmentioning

confidence: 99%

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DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

et al. 2020

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Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism. Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay. Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-a and IL-1b, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelialmesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results. Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

et al. 2020

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“…A recent study showed that in a DN rat model, overexpressing miR-218 was sufficient to reduce renal injury through regulating NF-κB-mediated inflammation. Moreover, they confirmed that miR-218 targets the messenger RNA (mRNA) encoding IKK-β [40]. [46].…”

Section: Characteristics Of Ncrnasmentioning

confidence: 86%

Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy

Mai

et al. 2020

Journal of Diabetes Research

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The correlation between diabetes and systematic well-being on human life has long established. As a common complication of diabetes, the prevalence of diabetic nephropathy (DN) has been increasing globally. DN is known to be a major cause of end-stage kidney disease (ESKD). Till now, the molecular mechanisms for DN have not been fully explored and the effective therapies are still lacking. Noncoding RNAs are a class of RNAs produced by genome transcription that cannot be translated into proteins. It has been documented that ncRNAs participate in the pathogenesis of DN by regulating inflammation, apoptosis, autophagy, cell proliferation, and other pathological processes. In this review, the pathological roles and diagnostic and therapeutic potential of three types of ncRNAs (microRNA, long noncoding RNA, and circular RNA) in the progression of DN are summarized and illustrated.

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“…Regarding miR-218, Yao et al [ 22 ] reported that microRNA-218 inhibited the viability and accelerates the apoptosis in ARPE-19 cells by directly targeting RUNX2. Moreover, the experimental research showed [ 23 ] that miR-218 was markedly downregulated in diabetic nephropathy rat model, and overexpressed miR-218 markedly reduced inflammatory responses, detected by measuring the level of TNF-α, IL-6, IL-1β, and MCP-1. Previously, it [ 24 ] has been reported that lncRNA CCAT1 serves as a microRNA-218 sponge to induce Gefitinib Resistance in NSCLC by Targeting HOXA1.…”

Section: Introductionmentioning

confidence: 99%

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

Pan

Zhang²,

Tang³

et al. 2020

Cancer Cell Int

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Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS.

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miR‐218 regulates diabetic nephropathy via targeting IKK‐β and modulating NK‐κB‐mediated inflammation

Cited by 40 publications

References 42 publications

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy

The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

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