Identification and validation of key long non-coding RNAs in resveratrol protect against IL-1β-treated chondrocytes via integrated bioinformatic analysis

Abstract

Background Long non-coding RNAs (lncRNAs) participate in regulation of gene transcription, but little is known about the correlation among resveratrol and lncRNAs. This study aimed to identify and validate the key lncRNAs in resveratrol protect against IL-1β-treated chondrocytes. Methods In this experiment, high-throughput sequencing technique was performed to identify the differentially expressed lncRNAs, miRNAs, and mRNAs between IL-1β-treated chondrocytes with or not resveratrol. Moreover, gene ontology and KEGG pathway of the differentially expressed genes were carried out by R software. Then, lncRNA-miRNA-mRNA network was constructed by Cytoscape software. Venn diagram was performed to identify the potentially target miRNAs of LINC00654. Then, real-time polymerase chain reaction (RT-PCR) was performed to validate the most significantly differentially expressed lncRNAs. Results Totally, 1016 differentially expressed lncRNAs were identified (493 downregulated) between control and resveratrol-treated chondrocytes. Totally, 75 differentially expressed miRNAs were identified (downregulated = 54, upregulated = 21). Totally, 3308 differentially expressed miRNAs were identified (downregulated = 1715, upregulated = 1593). GO (up) were as follows: skin development, response to organophosphorus. GO (down) mainly included visual perception, single fertilization, and sensory perception of smell. KEGG (up) were as follows: TNF signaling pathway and TGF-beta signaling pathway. KEGG (down) were as follows: viral protein interaction with cytokine and cytokine receptor. We identified that LINC00654 and OGFRL1 were upregulated in resveratrol-treated chondrocytes. However, miR-210-5p was downregulated in resveratrol-treated chondrocytes. Conclusion In sum, the present study for the first time detected the differential expressed lncRNAs involved in resveratrol-treated chondrocytes via employing bioinformatic methods.

Protective Effect of Resveratrol on Knee Osteoarthritis and its Molecular Mechanisms: A Recent Review in Preclinical and Clinical Trials

“…Additionally, it has been shown that lncRNAs function in regulating KOA apoptosis and are essential targets for the anti-apoptotic activity of RES ( Liu et al, 2018 ; Li et al, 2020 ; Xie et al, 2020 ). Yi et al found that RES can improve apoptosis of KOA chondrocytes by regulating LINC00654, which is believed to be a prospective target for ameliorating KOA ( Yi et al, 2021 ). The above in vitro evidence confirms that RES is considered a promising complementary therapeutic agent for treating KOA by acting on different in vitro chondrocyte models.…”

Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications

“…High-throughput RNA sequencing of chondrocytes treated with the pro-inflammatory factor IL-1beta, in presence or absence of resveratrol, revealed several differentially expressed lncRNAs, miRNAs, and mRNAs. ( Yi et al, 2021 ). Moreover, combining bioinformatics methods with RT-PCR validation, a competitive endogenous RNA (ceRNA) network, involving the lncRNA LINC00654, miR-210-5p, and the Opioid Growth Factor Receptor Like 1 (OGFRL1), was identified ( Yi et al, 2021 ).…”

“…( Yi et al, 2021 ). Moreover, combining bioinformatics methods with RT-PCR validation, a competitive endogenous RNA (ceRNA) network, involving the lncRNA LINC00654, miR-210-5p, and the Opioid Growth Factor Receptor Like 1 (OGFRL1), was identified ( Yi et al, 2021 ). In this network, the mutual interaction between lncRNAs and miRNAs may influence cellular metabolic activity and functions as lncRNAs may competitively bind miRNAs, weakening the miRNA responses on the mRNA target and regulating genes at the post-transcriptional level ( Yi et al, 2021 ).…”

“…Moreover, combining bioinformatics methods with RT-PCR validation, a competitive endogenous RNA (ceRNA) network, involving the lncRNA LINC00654, miR-210-5p, and the Opioid Growth Factor Receptor Like 1 (OGFRL1), was identified ( Yi et al, 2021 ). In this network, the mutual interaction between lncRNAs and miRNAs may influence cellular metabolic activity and functions as lncRNAs may competitively bind miRNAs, weakening the miRNA responses on the mRNA target and regulating genes at the post-transcriptional level ( Yi et al, 2021 ). Resveratrol treatment upregulated LINC00654 and OGFRL1 and downregulated miR-210-5p in chondrocytes, suggesting that LINC00654 acts as ceRNA by competitively occupying the shared binding sequences of miR-210-5p in the OGFRL1 mRNA, ultimately affecting its gene expression ( Yi et al, 2021 ).…”

“…In this network, the mutual interaction between lncRNAs and miRNAs may influence cellular metabolic activity and functions as lncRNAs may competitively bind miRNAs, weakening the miRNA responses on the mRNA target and regulating genes at the post-transcriptional level ( Yi et al, 2021 ). Resveratrol treatment upregulated LINC00654 and OGFRL1 and downregulated miR-210-5p in chondrocytes, suggesting that LINC00654 acts as ceRNA by competitively occupying the shared binding sequences of miR-210-5p in the OGFRL1 mRNA, ultimately affecting its gene expression ( Yi et al, 2021 ). Another association between resveratrol and miRNA has been identified by Song et al ( Song et al, 2016 ) in human THP-1 macrophages.…”