MicroRNA-122-5p ameliorates tubular injury in diabetic nephropathy via FIH-1/HIF-1α pathway

Li, Cheng; Qiu, Xinying; He, Liyu; Liu, Li

doi:10.1080/0886022x.2022.2039194

Cited by 13 publications

(8 citation statements)

References 51 publications

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“…About 20%–40% of diabetes can progress to DN ( 1 ). It is a leading contributor of DN to kidney failure in developed countries ( 17 , 18 ). Therefore, early diagnosis and intervention in DN are particularly important.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Zhou

Lin²,

Yang³

et al. 2023

Front. Immunol.

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BackgroundThe study aimed to identify core biomarkers related to diagnosis and immune microenvironment regulation and explore the immune molecular mechanism of diabetic nephropathy (DN) through bioinformatics analysis.MethodsGSE30529, GSE99325, and GSE104954 were merged with removing batch effects, and different expression genes (DEGs) were screened at a criterion |log2FC| >0.5 and adjusted P <0.05. KEGG, GO, and GSEA analyses were performed. Hub genes were screened by conducting PPI networks and calculating node genes using five algorithms with CytoHubba, followed by LASSO and ROC analysis to accurately identify diagnostic biomarkers. In addition, two different GEO datasets, GSE175759 and GSE47184, and an experiment cohort with 30 controls and 40 DN patients detected by IHC, were used to validate the biomarkers. Moreover, ssGSEA was performed to analyze the immune microenvironment in DN. Wilcoxon test and LASSO regression were used to determine the core immune signatures. The correlation between biomarkers and crucial immune signatures was calculated by Spearman analysis. Finally, cMap was used to explore potential drugs treating renal tubule injury in DN patients.ResultsA total of 509 DEGs, including 338 upregulated and 171 downregulated genes, were screened out. “chemokine signaling pathway” and “cell adhesion molecules” were enriched in both GSEA and KEGG analysis. CCR2, CX3CR1, and SELP, especially for the combination model of the three genes, were identified as core biomarkers with high diagnostic capabilities with striking AUC, sensitivity, and specificity in both merged and validated datasets and IHC validation. Immune infiltration analysis showed a notable infiltration advantage for APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. In addition, the correlation analysis showed that CCR2, CX3CR1, and SELP were strongly and positively correlated with checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. Finally, dilazep was screened out as an underlying compound for DN analyzed by CMap.ConclusionsCCR2, CX3CR1, and SELP are underlying diagnostic biomarkers for DN, especially in their combination. APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation may participate in the occurrence and development of DN. At last, dilazep may be a promising drug for treating DN.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Zhou

Lin²,

Yang³

et al. 2023

Front. Immunol.

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“…Furthermore, the correlation between miR-122-5p and p53 in clinical samples, combined with the analysis of the luciferase experimental report in the previous study [ 7 ], revealed that p53 was the direct regulatory target of miR-122-5p. Previous studies showed that some proteins, including α-smooth muscle actin [ 27 ] and hypoxia-inducible factor-1 [ 28 ] could be the active sites of miR-122-5p. Our study provided a new research idea for the applying of miR-122-5p.…”

Section: Discussionmentioning

confidence: 99%

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

et al. 2023

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The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

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“…The target reporter assay was conducted as shown in other study [ 11 , 20 ]. Briefly, 3′-UTR of the mouse IL-6 gene was synthesized and inserted into the pMIR-REPORT Luciferase plasmid (Life Technologies).The plasmids were cotransfected with pMIR-REPORT β-gal control plasmid and 200 nM miR-26a-5p mimics into HEK293 cells.…”

Section: Methodsmentioning

confidence: 99%

“…The quantitative real-time PCR was performed as described in other study [ 20 ]. Briefly, total RNAs were isolated from cultured BUMPT cells or kidney tissues with the TRIzol (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

Chen

Zhou

2022

Renal Failure

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Sepsis-induced acute kidney injury (AKI) is a common and life-threatening complication in hospitalized and critically ill patients and has unacceptable morbidity and mortality rates. However, effective approaches for the diagnosis and treatment of septic AKI are still lacking. Here, we demonstrated significant increases in the miR-26a-5p levels in renal tubular cells of LPS-induced septic AKI models both in vivo and in vitro . Mechanistically, we provided evidence of the involvement of NF-κB in miR-26a-5p induction. LPS treatment of renal tubular cells led to the activation of NF-κB, and inhibition of NF-κB by TPCA-1 prevented the induction of miR-26a-5p. These results indicated that NF-κB was a key upstream factor for the induction of miR-26a-5p in septic AKI. Anti-miR-26a-5p enhanced the expression of IL-6 at both the protein and mRNA levels following LPS treatment. Furthermore, our luciferase microRNA target reporter assay verified that IL-6 is a direct target of miR-26a-5p. Blocking miR-26a-5p promoted renal inflammation and worsened kidney injury. Thus, our study indicated that the miR-26a-5p/IL-6 axis can alleviate sepsis-induced acute kidney injury by inhibiting renal inflammation. This mechanism may represent a therapeutic target for septic AKI.

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MicroRNA-122-5p ameliorates tubular injury in diabetic nephropathy via FIH-1/HIF-1α pathway

Cited by 13 publications

References 51 publications

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

The miR-26a-5p/IL-6 axis alleviates sepsis-induced acute kidney injury by inhibiting renal inflammation

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