LincRNA 1700020I14Rik alleviates cell proliferation and fibrosis in diabetic nephropathy via miR-34a-5p/Sirt1/HIF-1α signaling

Li, Ailing; Peng, Rui; Sun, Yan; Liu, Handeng; Peng, Huimin; Zhang, Zheng

doi:10.1038/s41419-018-0527-8

Cited by 128 publications

(121 citation statements)

References 42 publications

(51 reference statements)

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“…This 38 Here we report the pathogenic effect of P53 on diabetic aortic endothelial dysfunction, with miR-34a to be the mediator. 39,40 As P53/ miR-34a activation leads to DM and its complications, inhibition of P53/miR-34a may produce beneficial effects on multiple organs/tissues in diabetic individuals. 39,40 As P53/ miR-34a activation leads to DM and its complications, inhibition of P53/miR-34a may produce beneficial effects on multiple organs/tissues in diabetic individuals.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of P53/miR‐34a improves diabetic endothelial dysfunction via activation of SIRT1

Wang

Tian

et al. 2019

J Cellular Molecular Medi

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Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)‐treated endothelial cells (ECs) were subjected to pifithrin‐α (PFT‐α)—a specific inhibitor of P53, or P53 ‐small interfering RNA (siRNA), both of which attenuated the HG‐induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT‐α or P53 ‐siRNA prohibited P53 acetylation, decreased microRNA‐34a (miR‐34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR‐34a inhibitor (miR‐34a‐I) and PFT‐α increased SIRT1 protein level and alleviated the HG‐induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT‐α were completely abrogated by the miR‐34a mimic. In addition, SIRT1 inhibition by EX‐527 or Sirt1 ‐siRNA completely abolished miR‐34a‐I's protection against HG‐induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin‐induced diabetic mice, both PFT‐α and miR‐34a‐I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycaemia. Hence, the present study has uncovered a P53/miR‐34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR‐34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Inhibition of P53/miR‐34a improves diabetic endothelial dysfunction via activation of SIRT1

Wang

Tian

et al. 2019

J Cellular Molecular Medi

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“…Cells were divided into 2 groups: high-glucose group (H-MC) (cells cultured with high glucose; 25 mM glucose) and low-glucose group (L-MC) (cells cultured with low glucose; 5.5 mM glucose and 19.5 mM mannitol). The high-glucose condition simulates the diabetic environment, whereas the low-glucose condition simulates a normal growth status (11,21). The overexpression plasmid of H2k2, named H2k2(+), was synthesized by Thermo Fisher Scientific.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…The lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) can regulate cell apoptosis of renal tubular epithelial cells in DN rats via miR-23c and the target gene embryonic lethal, abnormal vision-like 1 (ELAVL1) (10). Our previous study also showed the lncRNA 1700020I14Rik mediates the hypoxia-inducible factor 1a signaling pathway through miR-34a-5p and the target gene Sirtuin 1, thereby improving fibrosis and proliferation of MCs in DN (11). These findings suggest that ceRNA may be an important mechanism for lncRNAs in DN.…”

mentioning

confidence: 95%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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Evidence has shown that long noncoding RNAs (IncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of IncRNAs on mesangial cell (MC) proliferation in DN‐related ceRNA networks. Differences in IncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA‐seq, and DN‐related IncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real‐time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5‐ethynyl‐2′‐deoxyuridine (EdU) in MCs cultured under high‐ or low‐glucose conditions. Moreover, the effect of the topological key IncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)‐449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 IncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN‐related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of IncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA‐seq and real‐time qPCR in vivo and in vitro. miR‐449a and miR‐449b, which were down‐regulated in MCs cultured with high glucose, were selected for further analysis. The results of real‐time qPCR and luciferase assay revealed the IncRNA H2k2‐miR‐449a/b‐Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR‐449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key IncRNA H2k2 in the DN‐related ceRNA network and the miR‐449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.—Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key IncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR‐449a/b/Trim11/Mek signaling pathway. FASEB J. 33, 11492–11506 (2019). http://www.fasebj.org

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“…Also, we assessed the expression of ZBTB2 in cell lines, finding that ZBTB2 was significantly upregulated in four ESCC cell lines compared with the normal cells (Figure A). Previous studies have revealed that ZBTB2 is a master activator of the p53 pathway, involving important cell cycle‐related genes and tumor suppressor genes which play significant roles in tumor progression in numerous human cancers, including in ESCC . Therefore, we further investigated whether miR‐488‐3p could regulate p53 signaling through ZBTB2.…”

Section: Resultsmentioning

confidence: 98%

MicroRNA‐488‐3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma

Yang

et al. 2019

J of Cellular Biochemistry

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Esophageal squamous cell carcinoma (ESCC) is the eighth most prevalent cancer and the sixth leading cause for cancer‐associated mortality. MicroRNAs (miRNAs) are increasingly reported to exert important regulatory functions in human cancers by regulating certain gene expression. miR‐488‐3p has been identified to be a tumor suppressor in multiple cancers, but its role in ESCC is yet to be investigated. The present study aimed to uncover the biological role and modulatory mechanism of miR‐488‐3p in ESCC. We first revealed the downregulation of miR‐488‐3p in ESCC tissues and cell lines. Gain‐of‐function assays confirmed that miR‐488‐3p overexpression abrogated proliferation and accelerated apoptosis. Mechanistically, we identified via bioinformatics tool and confirmed that zinc finger and BTB domain containing 2 (ZBTB2) was a target for miR‐488‐3p. Moreover, miR‐488‐3p activated the p53 pathway through suppressing ZBTB2. Finally, rescue assays proved that ZBTB2 was involved in the regulation of miR‐488‐3p on proliferation and apoptosis in ESCC. Additionally, we verified that miR‐488‐3p had alternate targets in ESCC by confirming the involvement of protein kinase, DNA‐activated, catalytic subunit (PRKDC), a known target for miR‐488‐3p, in miR‐488‐3p‐mediated regulation on ESCC. In sum, this study revealed that miR‐488‐3p inhibited proliferation and induced apoptosis by targeting ZBTB2 and activating p53 pathway in esophageal squamous cell carcinoma, providing a novel biological target for ESCC.

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LincRNA 1700020I14Rik alleviates cell proliferation and fibrosis in diabetic nephropathy via miR-34a-5p/Sirt1/HIF-1α signaling

Cited by 128 publications

References 42 publications

Inhibition of P53/miR‐34a improves diabetic endothelial dysfunction via activation of SIRT1

Inhibition of P53/miR‐34a improves diabetic endothelial dysfunction via activation of SIRT1

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

MicroRNA‐488‐3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma

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