scholarly journals METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Liping Meng ◽  
Hui Lin ◽  
Xingxiao Huang ◽  
Jingfan Weng ◽  
Fang Peng ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Epigenetic Regulation ◽  
Mrna Stability ◽  
Regulatory Mechanism ◽  
Rat Tissues ◽  
The Novel ◽  
Related Protein ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation

AbstractN6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.

scholarly journals METTL14 Suppresses Pyroptosis and Diabetic Cardiomyopathy by Down-Regulating TINCR lncRNA

2021 ◽  
Author(s):  
Liping Meng ◽  
Hui Lin ◽  
Xingxiao Huang ◽  
Jingfan Wen ◽  
Shengjie Wu
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Epigenetic Regulation ◽  
Regulatory Mechanism ◽  
Rat Tissues ◽  
The Novel ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation

Abstract Background: N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression.Methods: DCM rat model was established and qRT-PCR, western blot and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction.Results: In vivo and in vitro studies showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 through increasing its mRNA stability.Conclusions: Our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.

scholarly journals LncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Panpan Liu ◽  
Lei Zhao ◽  
Yuxia Gu ◽  
Meilan Zhang ◽  
Hongchang Gao ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interstitial Lung Diseases ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation ◽  
And Migration

Abstract Background Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung diseases with a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to be involved in IPF in several studies. However, the role of lncRNA SNHG16 in IPF is largely unknown. Methods Firstly, experimental pulmonary fibrosis model was established by using bleomycin (BML). Histology and Western blotting assays were used to determine the different stages of fibrosis and expression of several fibrosis biomarkers. The expression of SNHG16 was detected by quantitative real-time polymerase chain reaction (qRT‐PCR). EdU staining and wound-healing assay were utilized to analyze proliferation and migration of lung fibroblast cells. Molecular mechanism of SNHG16 was explored by bioinformatics, dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and qRT-PCR. Results The expression of SNHG16 was significantly up-regulated in bleomycin-(BLM) induced lung fibrosis and transforming growth factor-β (TGF-β)-induced fibroblast. Knockdown of SNHG16 could attenuate fibrogenesis. Mechanistically, SNHG16 was able to bind and regulate the expression of miR-455-3p. Moreover, SNHG16 also regulated the expression of Notch2 by targeting miR-455-3p. Finally, SNHG16 could promote fibrogenesis by regulating the expression of Notch2. Conclusion Taken together, our study demonstrated that SNHG16 promoted pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. These findings might provide a novel insight into pathologic process of lung fibrosis and may provide prevention strategies in the future.

scholarly journals IL-35 subunit EBI3 alleviates bleomycin-induced pulmonary fibrosis via suppressing DNA enrichment of STAT3

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Donghong Chen ◽  
Guofeng Zheng ◽  
Qing Yang ◽  
Le Luo ◽  
Jinglian Shen
Keyword(s):  
Gene Expression ◽  
Pulmonary Fibrosis ◽  
Regulatory Mechanism ◽  
Lung Epithelial Cells ◽  
Wild Type ◽  
Qrt Pcr ◽  
Lung Epithelial ◽  
Gene Expression Analyses ◽  
Human And Mouse

Abstract Background IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Methods Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. Results IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. Conclusion IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.

scholarly journals METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ben Yue ◽  
Chenlong Song ◽  
Linxi Yang ◽  
Ran Cui ◽  
Xingwang Cheng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation ◽  
E Cadherin

Abstract Background As one of the most frequent chemical modifications in eukaryotic mRNAs, N6-methyladenosine (m6A) modification exerts important effects on mRNA stability, splicing, and translation. Recently, the regulatory role of m6A in tumorigenesis has been increasingly recognized. However, dysregulation of m6A and its functions in tumor epithelial-mesenchymal transition (EMT) and metastasis remain obscure. Methods qRT-PCR and immunohistochemistry were used to evaluate the expression of methyltransferase-like 3 (METTL3) in gastric cancer (GC). The effects of METTL3 on GC metastasis were investigated through in vitro and in vivo assays. The mechanism of METTL3 action was explored through transcriptome-sequencing, m6A-sequencing, m6A methylated RNA immunoprecipitation quantitative reverse transcription polymerase chain reaction (MeRIP qRT-PCR), confocal immunofluorescent assay, luciferase reporter assay, co-immunoprecipitation, RNA immunoprecipitation and chromatin immunoprecipitation assay. Results Here, we show that METTL3, a major RNA N6-adenosine methyltransferase, was upregulated in GC. Clinically, elevated METTL3 level was predictive of poor prognosis. Functionally, we found that METTL3 was required for the EMT process in vitro and for metastasis in vivo. Mechanistically, we unveiled the METTL3-mediated m6A modification profile in GC cells for the first time and identified zinc finger MYM-type containing 1 (ZMYM1) as a bona fide m6A target of METTL3. The m6A modification of ZMYM1 mRNA by METTL3 enhanced its stability relying on the “reader” protein HuR (also known as ELAVL1) dependent pathway. In addition, ZMYM1 bound to and mediated the repression of E-cadherin promoter by recruiting the CtBP/LSD1/CoREST complex, thus facilitating the EMT program and metastasis. Conclusions Collectively, our findings indicate the critical role of m6A modification in GC and uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against GC.

scholarly journals HOXA-AS2 Promotes Glioblastoma Carcinogenesis by Targeting miR-885-5p Thus Releasing RBBP4 mRNA

2020 ◽  
Author(s):  
Jixin Shou ◽  
Haidong Gao ◽  
Sen Cheng ◽  
Bingbing Wang ◽  
Haibo Guan
Keyword(s):  
Regulatory Mechanism ◽  
Luciferase Assay ◽  
Glioblastoma Cells ◽  
Promoting Effect ◽  
Positive Role ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Brdu Assay ◽  
Rip Assay

Abstract Background: HOXA-AS2, a lncRNA, had been proved to exert the promoting effect on glioblastoma, but its regulatory mechanism was not fully revealed. Our study focused on the interaction and role of HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma. Methods: qRT-PCR was used to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual luciferase assay, RIP assay and RNA pull-down assay were applied to reveal the interaction among HOXA-AS2, miR-885-5p and RBBP4. The cell functional experiments such as CCK-8, BrdU assay and cell adhesion etc. were used to analyze the effect of HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma cells. Results: HOXA-AS2 and RBBP4 were overexpressed in 33 glioblastoma tissue samples and glioblastoma cells, as well as HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. On the other hand, miR-885-5p was proved to be down-regulated in 33 glioblastoma tissue samples and glioblastoma cells, and it was an obstacle to the malignant phenotypes of glioblastoma cells. Meanwhile, HOXA-AS2 could negative regulate miR-885-5p, thereby promoting the RBBP4 expression since RBBP4 was targeted by miR-885-5p. Finally, HOXA-AS2 was proved to act as the positive role in glioblastoma cells via negative regulating miR-885-5p to release RBBP4.Conclusion: HOXA-AS2 promotes the tumorigenesis of glioblastoma through targeting miR-885-5p to induce the RBBP4 expression.

scholarly journals Knockdown of LINC01694 inhibits growth of gallbladder cancer cells via miR-340-5p/Sox4

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Lei Liu ◽  
Yuexiang Yan ◽  
Guanyu Zhang ◽  
Chengxue Chen ◽  
Weihong Shen ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
High Mobility ◽  
Tumor Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation

Abstract Purpose: The indispensable role of long non-coding RNAs (lncRNAs) in tumorigenesis has been increasingly reported. In the present study, LINC01694 was found to regulate the proliferation, invasion, as well as apoptosis in gallbladder cancer (GBC) cells through sponging miR-340-5p. Methods: LINC01694 level in GBC cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, invasion, and apoptosis were determined by Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. The expression of Sry-related high-mobility group box 4 (Sox4) was detected by Western blot (WB). The interaction between LINC01694 and miR-340-5p was measured by dual-luciferase reporter (DLR) assay, RNA immunoprecipitation (RIP) test, and RNA pull-down. Tumor formation was examined by in vivo experiment. Results: qRT-PCR illustrated that cancerous tissues had higher LINC01694 than normal tissues. Survival analysis demonstrated that the prognosis of patients with high LINC01694 was significantly poorer than those with low LINC01694. Down-regulation of LINC01694 slowed down the proliferation and invasion in GBC cells and accelerated the apoptosis. DLR assay indicated that LINC01694 elevated Sox4 expression by regulating miR-340-5p. LINC01694 functioned as miR-340-5p sponge to inhibit Sox4 expression. Conclusion: LINC01694 level is elevated in GBC by regulating miR-340-5p/Sox4 axis, which indicates the poor prognosis of the patients.

scholarly journals LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis

2020 ◽  
Author(s):  
Jixin Shou ◽  
Haidong Gao ◽  
Sen Cheng ◽  
Bingbing Wang ◽  
Haibo Guan
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Regulatory Mechanism ◽  
Luciferase Assay ◽  
Pcr Analysis ◽  
Western Blot Assay ◽  
Qrt Pcr ◽  
Brdu Assay ◽  
Rip Assay

Abstract Background: LncRNA HOXA-AS2 has been found in the literature to deteriorate glioblastoma. However, its regulatory mechanism is yet to be fully investigated. Our study focused chiefly on the interaction and role of the HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma. Methods: qRT-PCR analysis was performed to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual-luciferase assay, RIP assay and RNA pull-down assay were later carried out to reveal the interactions among HOXA-AS2, miR-885-5p and RBBP4. After that, CCK-8 assay, BrdU assay, nude mice xenografting assay, western blot assay, and flow cytometry were carried out to analyze the effect of the HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma samples. Results: HOXA-AS2 and RBBP4 were found to be overexpressed in glioblastoma. Experimental results showed that HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. However, miR-885-5p was observed to be downregulated in glioblastoma. Findings also indicated that HOXA-AS2 could negatively regulate miR-885-5p, thereby enhancing RBBP4 expression. Conclusion: Overall, HOXA-AS2 promoted the tumorigenesis of glioblastoma by targeting and regulating miR-885-5p to induce the expression of RBBP4.

scholarly journals The Role of Anti-Inflammatory Adipokines in Cardiometabolic Disorders: Moving beyond Adiponectin

2021 ◽  
Vol 22 (24) ◽  
pp. 13529
Author(s):  
Han Na Jung ◽  
Chang Hee Jung
Keyword(s):  
Metabolic Disorders ◽  
Current Evidence ◽  
Cardiometabolic Health ◽  
The Novel ◽  
Related Protein ◽  
Inflammatory Conditions ◽  
Extra Energy ◽  
Cardiometabolic Disorders ◽  
Anti Inflammatory

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.

scholarly journals LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis

2020 ◽  
Author(s):  
Jixin Shou ◽  
Haidong Gao ◽  
Sen Cheng ◽  
Bingbing Wang ◽  
Haibo Guan
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Regulatory Mechanism ◽  
Luciferase Assay ◽  
Pcr Analysis ◽  
Western Blot Assay ◽  
Qrt Pcr ◽  
Brdu Assay ◽  
Rip Assay

Abstract Background: LncRNA HOXA-AS2 has been found in the literature to deteriorate glioblastoma. However, its regulatory mechanism is yet to be fully investigated. Our study focused chiefly on the interaction and role of the HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma. Methods: qRT-PCR analysis was performed to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual-luciferase assay, RIP assay and RNA pull-down assay were later carried out to reveal the interactions among HOXA-AS2, miR-885-5p and RBBP4. After that, CCK-8 assay, BrdU assay, nude mice xenografting assay, western blot assay, and flow cytometry were carried out to analyze the effect of the HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma samples. Results: HOXA-AS2 and RBBP4 were found to be overexpressed in glioblastoma. Experimental results showed that HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. However, miR-885-5p was observed to be downregulated in glioblastoma. Findings also indicated that HOXA-AS2 could negatively regulate miR-885-5p, thereby enhancing RBBP4 expression. Conclusion: Overall, HOXA-AS2 promoted the tumorigenesis of glioblastoma by targeting and regulating miR-885-5p to induce the expression of RBBP4.

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