Fructose downregulates miR‐330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin

Gu, Ting-Ting; Song, Lin; Chen, Tianyu; Wang, Xing; Zhao, Xiaojuan; Ding, Xiaoqin; Yang, Yichen; Pan, Ying; Zhang, Dongmei; Kong, Ling-Dong

doi:10.1002/mnfr.201600760

Cited by 41 publications

(22 citation statements)

References 59 publications

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“…An association between hsa‐mir‐330 and cancer has already been described. This miRNA seems to play an oncogenic role in human glioblastoma (Qu et al ., ) and is involved in the inflammatory response (Gu et al ., ). Recent data by Hu et al .…”

Section: Discussionmentioning

confidence: 91%

Epigenetic events involved in organic cation transporter 1‐dependent impaired response of hepatocellular carcinoma to sorafenib

Al-Abdulla

Lozano

Macı́as

et al. 2019

British J Pharmacology

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Background and Purpose The expression of the human organic cation transporter‐1 (hOCT1, gene SLC22A1) is reduced in hepatocellular carcinoma (HCC). The molecular bases of this reduction and its relationship with the poor response of HCC to sorafenib were investigated. Experimental Approach HCC transcriptomes from 366 samples available at TCGA were analysed. Alternative splicing was determined by RT‐PCR. The role of miRNAs in SLC22A1 downregulation was investigated. Expression of Oct1 was measured in rodent HCC models (spontaneously generated in Fxr‐/‐ mice and chemically‐induced in rats). hOCT1 was overexpressed in human hepatoma cells (HuH7 and HepG2). Sorafenib and regorafenib uptake was determined by HPLC‐MS/MS. Key Results hOCT1 overexpression enhanced sorafenib, but not regorafenib, quinine‐inhibitable uptake by hepatoma cells. In rodent HCC, Oct1 was downregulated, which was accompanied by impaired sorafenib uptake. In mice with s.c.‐implanted HCC, sorafenib inhibited the growth of hOCT1 overexpressing tumours. In human HCC, hOCT1 expression was inversely correlated with SLC22A1 promoter methylation, whereas demethylation with decitabine enhanced hOCT1 expression in hepatoma cells. Increased proportion of aberrant hOCT1 mRNA variants was found in HCC samples. In silico analysis identified six miRNAs as candidates to target hOCT1 mRNA. When overexpressed in HepG2 cells a significant hOCT1 mRNA decay was induced by hsa‐miR‐330 and hsa‐miR‐1468. Analysis of 39 paired tumour/adjacent samples from TCGA revealed that hsa‐mir‐330 was consistently upregulated in HCC. Conclusion and Implications Impaired hOCT1 expression/function in HCC, in part due to epigenetic modifications, plays an important role in the poor pharmacological response of this cancer to sorafenib.

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Section: Discussionmentioning

confidence: 91%

Epigenetic events involved in organic cation transporter 1‐dependent impaired response of hepatocellular carcinoma to sorafenib

Al-Abdulla

Lozano

Macı́as

et al. 2019

British J Pharmacology

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“…All rats were fed with standard pellets ad libitum for 6 weeks. The normal group received normal drinking water, while fructose and CLA groups were given drinking water with 10% fructose for 6 weeks to induce hyperuricemia, insulin resistance, and renal inflammation . Distilled water and CLA were given orally once a day at 14:00–15:00.…”

Section: Methodsmentioning

confidence: 99%

Conjugated Linoleic Acid Ameliorates High Fructose‐Induced Hyperuricemia and Renal Inflammation in Rats via NLRP3 Inflammasome and TLR4 Signaling Pathway

Tan

Wan

Chen

et al. 2019

Molecular Nutrition Food Res

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Scope: Conjugated linoleic acid (CLA), a bioactive substance predominantly found in ruminant products, improves insulin resistance and exhibits anti-inflammatory activity. The chief objective of the study is to investigate the effects and potential mechanisms of CLA on high fructose-induced hyperuricemia and renal inflammation. Methods and results: Hyperuricemia and renal inflammation are induced in rats by 10% fructose. Hyperuricemia, insulin resistance, and renal inflammation are evaluated. CLA potently ameliorates fructose-induced hyperuricemia with insulin resistance and significantly reduces the levels of inflammation factors in serum and kidney. It reverses fructose-induced upregulation of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in the kidney. Moreover, CLA dramatically inhibits the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Additionally, CLA suppresses toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling activation to inhibit nuclear factor-kB (NF-kB) signaling in the kidney of fructose-fed rats. Conclusion: CLA ameliorates hyperuricemia along with insulin resistance and renal inflammatory, which may be associated with the suppression of renal GLUT9 and URAT1 in fructose-fed rats. Its molecular mechanism may be related to the inhibition of NLRP3 inflammasome and TLR4/MyD88 signaling pathway. Therefore, CLA may be a promising candidate for preventing fructose-induced hyperuricemia and renal inflammation.

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“…Administration of miR-330-3p mimics attenuates fructoseinduced upregulation of SphK1, NF-kB, NLRP3, pro-IL-1b, and IL-1b protein levels, whereas miR-330-3p inhibition has the opposite effect in a proximal tubule epithelial cell line from adult human kidney (HK-2 cells) (70). By targeting SphK1, miR-330-3p thus inhibits inflammasome priming (70).…”

Section: Mirnas Modulate Inflammasome Regulationmentioning

confidence: 99%

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

Boxberger

Hecker

Zettl

2019

The Journal of Immunology

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Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1–mediated cleavage of the proinflammatory cytokines IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs that regulate gene expression posttranscriptionally. miRNAs, such as miR-223-3p, have been demonstrated to directly target the inflammasome components NLRP3, caspase-1, and caspase-8. Other miRNAs like miR-155-5p modulate TLR-, IL-1R–, TNFR-, and IFNAR-mediated signaling pathways upstream of the inflammasomes. In this study, we discuss how a more detailed elucidation of miRNA-driven inflammasome regulation helps in understanding the molecular processes underlying immune-mediated human diseases, holds potential for the identification of biomarkers and may offer novel targets for the development of future therapeutics.

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Fructose downregulates miR‐330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin

Cited by 41 publications

References 59 publications

Epigenetic events involved in organic cation transporter 1‐dependent impaired response of hepatocellular carcinoma to sorafenib

Epigenetic events involved in organic cation transporter 1‐dependent impaired response of hepatocellular carcinoma to sorafenib

Conjugated Linoleic Acid Ameliorates High Fructose‐Induced Hyperuricemia and Renal Inflammation in Rats via NLRP3 Inflammasome and TLR4 Signaling Pathway

Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases

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