The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Fan, Hai-Peng; Zhu, Zhixia; Xu, Jiajun; Li, Yutang; Guo, Chunwen; Hong, Yan

doi:10.1177/03000605211037495

Cited by 9 publications

(3 citation statements)

References 44 publications

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“…In an effort to evaluate the role of miR-424 in oxidative stress accumulation, an miR-424 inhibitor was applied, and we showed that ROS generation was suppressed. Our findings were consistent with another study showing that miR-424 conferred to the LPS-induced ROS production in lipopolysaccharide (LPS)-treated pulmonary alveolar epithelial cells [ 29 ] or LPS-stimulated proximal tubule epithelial cells [ 30 ]. However, miR-424 was revealed to abrogate oxidative stress-associated injury by increasing antioxidant enzymes and reducing oxidative stress indicators in C57/BL6 mice with transient cerebral ischemia [ 18 ].…”

Section: Discussionsupporting

confidence: 93%

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

Chou

Hsieh

Chao

et al. 2023

IJMS

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Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-β signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-β/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.

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Section: Discussionsupporting

confidence: 93%

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

Chou

Hsieh

Chao

et al. 2023

IJMS

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“…These 500 samples were then added to the LIME explainer and input to the HGC-GAN for prediction to assess the contribution level of the features. Through model predictions, the disease with the highest associated probability with CASC9 was identified as Acute Kidney Failure, and this association prediction has been confirmed [ 39 ]. Therefore, we conducted experimental analysis on the association between CASC9 and Acute Kidney Failure.…”

Section: Resultsmentioning

confidence: 96%

Predicting lncRNA-disease associations based on heterogeneous graph convolutional generative adversarial network

Lu,

Zhong,

Tang

et al. 2023

PLoS Comput Biol

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There is a growing body of evidence indicating the crucial roles that long non-coding RNAs (lncRNAs) play in the development and progression of various diseases, including cancers, cardiovascular diseases, and neurological disorders. However, accurately predicting potential lncRNA-disease associations remains a challenge, as existing methods have limitations in extracting heterogeneous association information and handling sparse and unbalanced data. To address these issues, we propose a novel computational method, called HGC-GAN, which combines heterogeneous graph convolutional neural networks (GCN) and generative adversarial networks (GAN) to predict potential lncRNA-disease associations. Specifically, we construct a lncRNA-miRNA-disease heterogeneous network by integrating multiple association data and sequence information. The GCN-based generator is then employed to aggregate neighbor information of nodes and obtain node embeddings, which are used to predict lncRNA-disease associations. Meanwhile, the GAN-based discriminator is trained to distinguish between real and fake lncRNA-disease associations generated by the generator, enabling the generator to improve its ability to generate accurate lncRNA-disease associations gradually. Our experimental results demonstrate that HGC-GAN performs better in predicting potential lncRNA-disease associations, with AUC and AUPR values of 0.9591 and 0.9606, respectively, under 10-fold cross-validation. Moreover, our case study further confirms the effectiveness of HGC-GAN in predicting potential lncRNA-disease associations, even for novel lncRNAs without any known lncRNA-disease associations. Overall, our proposed method HGC-GAN provides a promising approach to predict potential lncRNA-disease associations and may have important implications for disease diagnosis, treatment, and drug development.

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“…Wang et al found that XIST acts as a ceRNA for miRNA-155-5p to suppress inflammation and apoptosis, thereby attenuating sepsis-induced AKI( Wang and Cao, 2022 ). Furthermore, Fan et al found that the CASC9 could attenuate LPS-induced acute renal inflammatory injury via the miRNA-424-5p/TXNIP axis ( Fan et al, 2021 ). The latest research showed that NORAD knockdown alleviated kidney injury in mice and decreased the inflammatory response and apoptosis of LPS-stimulated HK-2 cells via the miRNA-577/GOLPH3 axis ( Xie et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The Intersection of Acute Kidney Injury and Non-Coding RNAs: Inflammation

Lin

Xia

et al. 2022

Front. Physiol.

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Acute renal injury (AKI) is a complex clinical syndrome, involving a series of pathophysiological processes, in which inflammation plays a key role. Identification and verification of gene signatures associated with inflammatory onset and progression are imperative for understanding the molecular mechanisms involved in AKI pathogenesis. Non-coding RNAs (ncRNAs), involved in epigenetic modifications of inflammatory responses, are associated with the aberrant expression of inflammation-related genes in AKI. However, its regulatory role in gene expression involves precise transcriptional regulation mechanisms which have not been fully elucidated in the complex and volatile inflammatory response of AKI. In this study, we systematically review current research on the intrinsic molecular mechanisms of ncRNAs that regulate the inflammatory response in AKI. We aim to provide potential research directions and strategies for developing ncRNA-targeted gene therapies as an intervention for the inflammatory damage in AKI.

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The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Cited by 9 publications

References 44 publications

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

Predicting lncRNA-disease associations based on heterogeneous graph convolutional generative adversarial network

The Intersection of Acute Kidney Injury and Non-Coding RNAs: Inflammation

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