SAIL: a new conserved anti-fibrotic lncRNA in the heart

Luo, Shenjian; Zhang, Mingyu; Wu, Hao; Ding, Xiaoyan; Li, Danyang; Dong, Xue; Hu, Xiaoxi; Su, Shuang; Shang, Wendi; Wu, Jiaxu; Hongwen, Xiao; Yang, Wanqi; Zhang, Qi; Zhang, Jifan; Lu, Yanjie; Pan, Zhenwei

doi:10.1007/s00395-021-00854-y

Cited by 34 publications

(24 citation statements)

References 49 publications

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“…The full name of SAFB is scaffold attachment factor B, which is highly conserved in evolution ( Luo et al, 2021 ). It was first identified through its ability to bind to DNA elements in the scaffold attachment region; however, more attention was subsequently given to RNA binding and protein–protein interaction ( Norman et al, 2016 ; Huo et al, 2020 ; Zhou et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

et al. 2021

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Background: Pancreatic adenocarcinoma (PAAD) has a considerably bad prognosis, and its pathophysiologic mechanism remains unclear. Thus, we aimed to identify real hub genes to better explore the pathophysiology of PAAD and construct a prognostic panel to better predict the prognosis of PAAD using the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithms.Methods: WGCNA identified the modules most closely related to the PAAD stage and grade based on the Gene Expression Omnibus. The module genes significantly associated with PAAD progression and prognosis were considered as the real hub genes. Eligible genes in the most significant module were selected for construction and validation of a multigene prognostic signature based on the LASSO-Cox regression analysis in The Cancer Genome Atlas and the International Cancer Genome Consortium databases, respectively.Results: The brown module identified by WGCNA was most closely associated with the clinical characteristics of PAAD. Scaffold attachment factor B (SAFB) was significantly associated with PAAD progression and prognosis, and was identified as the real hub gene of PAAD. Moreover, both transcriptional and translational levels of SAFB were significantly lower in PAAD tissues compared with normal pancreatic tissues. In addition, a novel multigene-independent prognostic signature consisting of SAFB, SP1, and SERTAD3 was identified and verified. The predictive accuracy of our signature was superior to that of previous studies, especially for predicting 3- and 5-year survival probabilities. Furthermore, a prognostic nomogram based on independent prognostic variables was developed and validated using calibration curves. The predictive ability of this nomogram was also superior to the well-established AJCC stage and histological grade. The potential mechanisms of different prognoses between the high- and low-risk subgroups were also investigated using functional enrichment analysis, GSEA, ssGSEA, immune checkpoint analysis, and mutation profile analysis.Conclusion: SAFB was identified as the real hub gene of PAAD. A novel multigene-independent prognostic signature was successfully identified and validated to better predict PAAD prognosis. An accurate nomogram was also developed and verified to aid in the accurate treatment of tumors, as well as in early intervention.

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Section: Discussionmentioning

confidence: 99%

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

et al. 2021

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“…The expression of miRNA is also regulated by epigenetic factors, such as DNA methylation, lncRNA, circRNA, and histone modification [ 22 , 53 – 59 ]. Many miRNAs are also regulated in posttranscriptional processing; for example, miRNAs are spliced by argonaute (AGO) proteins [ 60 ], Drosha [ 61 , 62 ], Dicer [ 63 ], silencing regulatory protein KRSP [ 64 ], and tristetraprolin (TTP) [ 64 ]. The stability of miRNA is another factor that affects its expression level.…”

Section: Ncrnamentioning

confidence: 99%

Epigenetic Changes and Functions in Pneumoconiosis

Cheng

Fan

et al. 2022

Oxidative Medicine and Cellular Longevity

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Pneumoconiosis is one of the most common occupational diseases in the world, and specific treatment methods of pneumoconiosis are lacking at present, so it carries great social and economic burdens. Pneumoconiosis, coronavirus disease 2019, and idiopathic pulmonary fibrosis all have similar typical pathological changes—pulmonary fibrosis. Pulmonary fibrosis is a chronic lung disease characterized by excessive deposition of the extracellular matrix and remodeling of the lung tissue structure. Clarifying the pathogenesis of pneumoconiosis plays an important guiding role in its treatment. The occurrence and development of pneumoconiosis are accompanied by epigenetic factors (e.g., DNA methylation and noncoding RNA) changes, which in turn can promote or inhibit the process of pneumoconiosis. Here, we summarize epigenetic changes and functions in the several kinds of evidence classification (epidemiological investigation, in vivo, and in vitro experiments) and main types of cells (macrophages, fibroblasts, and alveolar epithelial cells) to provide some clues for finding specific therapeutic targets for pneumoconiosis and even for pulmonary fibrosis.

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Section: Se Alleviates Homocysteine-induced Fibrosis In Cardiac Fibroblasts Via Downregulation Of Lncrna Meg3mentioning

confidence: 99%

“…Recent studies reported that some non-coding RNAs show great potential in the regulation of cardiac fibrosis (11)(12)(13). Long non-coding RNAs (lncRNAs) are a type of none-coding RNA of >200 nucleotides in length, which participate in various biological behavioral processes, including the onset and development of some cardiac diseases (12)(13)(14)(15)(16). The lncRNA scaffold attachment factor B interacting lncRNA (SAIL) has been shown to improve cardiac fibrosis after myocardial infarction by regulating the transcription of fibrosis-related genes, such as α-SMA, collagen I and Ⅲ (12,14).…”

Section: Se Alleviates Homocysteine-induced Fibrosis In Cardiac Fibroblasts Via Downregulation Of Lncrna Meg3mentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs) are a type of none-coding RNA of >200 nucleotides in length, which participate in various biological behavioral processes, including the onset and development of some cardiac diseases (12)(13)(14)(15)(16). The lncRNA scaffold attachment factor B interacting lncRNA (SAIL) has been shown to improve cardiac fibrosis after myocardial infarction by regulating the transcription of fibrosis-related genes, such as α-SMA, collagen I and Ⅲ (12,14). The lncRNA maternally expressed 3 (MEG3) has been reported to regulate cardiomyocyte proliferation and apoptosis (15,16).…”

Section: Se Alleviates Homocysteine-induced Fibrosis In Cardiac Fibroblasts Via Downregulation Of Lncrna Meg3mentioning

confidence: 99%

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Se alleviates homocysteine‑induced fibrosis in cardiac fibroblasts via downregulation of lncRNA MEG3

Cui

et al. 2021

Exp Ther Med

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Selenium (Se) is considered to have antioxidant properties, which are beneficial for heart condition. Hyperhomocysteinemia (HHCY) has been suggested to potentially lead to heart failure and is characterized by cardiac fibrosis; however, investigation on the role of Se and HHCY in cardiac fibrosis is rare. Since previous studies demonstrated the important role of the long non-coding RNA maternally expressed 3 (MEG3) in some heart diseases, the present study aimed to determine how Se and MEG3 might exert regulatory effects on HCY-induced fibrosis in cardiac fibroblasts (CFs). Mouse CFs were isolated and treated with HCY and Se. The expression of α-smooth muscle actin (α-SMA), collagen I and III was detected by western blotting to reflect CF fibrosis. Reverse transcription-quantitative PCR was performed to determine the expression levels of MEG3. Inflammation and oxidative stress responses were analyzed by measuring TNF-α, IL-1β (ELISA) and reactive oxygen species levels (using a commercial kit), respectively. Cell Counting Kit-8 was used to evaluate CF proliferation. Total and phosphorylated (p) expression of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was evaluated by western blotting. CFs were transfected with adenovirus expressing MEG3 short-hairpin RNA to knock down MEG3 expression. Se treatment downregulated the expression level of MEG3 in HCY-stimulated CFs, whilst inhibiting the inflammatory and oxidative stress response. Furthermore, Se inhibited the increased proliferation of CFs following HCY treatment. In addition, MEG3-knockdown in CFs could improve fibrosis caused by HCY. Furthermore, the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 were decreased following treatment with Se or MEG3 silencing. Taken together, the findings from the present study suggested that Se may alleviate cardiac fibrosis by downregulating the expression of MEG3 and reducing the inflammatory and oxidative stress response in CFs. This suggests that Se may be a potential therapeutic option for treating cardiac fibrosis in the future.

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SAIL: a new conserved anti-fibrotic lncRNA in the heart

Cited by 34 publications

References 49 publications

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

Epigenetic Changes and Functions in Pneumoconiosis

Se alleviates homocysteine‑induced fibrosis in cardiac fibroblasts via downregulation of lncRNA MEG3

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