scholarly journals The Impact of lncRNAs in Diabetes Mellitus: A Systematic Review and In Silico Analyses

2021 ◽  
Vol 12 ◽  
Author(s):  
Cristine Dieter ◽  
Natália Emerim Lemos ◽  
Nathalia Rodrigues de Faria Corrêa ◽  
Taís Silveira Assmann ◽  
Daisy Crispim

Long non-coding RNAs (lncRNAs) are non-coding transcripts that have emerged as one of the largest and diverse RNA families that regulate gene expression. Accumulating evidence has suggested a number of lncRNAs are involved in diabetes mellitus (DM) pathogenesis. However, results about lncRNA expressions in DM patients are still inconclusive. Thus, we performed a systematic review of the literature on the subject followed by bioinformatics analyses to better understand which lncRNAs are dysregulated in DM and in which pathways they act. Pubmed, Embase, and Gene Expression Omnibus (GEO) repositories were searched to identify studies that investigated lncRNA expression in cases with DM and non-diabetic controls. LncRNAs consistently dysregulated in DM patients were submitted to bioinformatics analysis to retrieve their target genes and identify potentially affected signaling pathways under their regulation. Fifty-three eligible articles were included in this review after the application of the inclusion and exclusion criteria. Six hundred and thirty-eight lncRNAs were differentially expressed between cases and controls in at least one study. Among them, six lncRNAs were consistently dysregulated in patients with DM (Anril, Hotair, Malat1, Miat, Kcnq1ot1, and Meg3) compared to controls. Moreover, these six lncRNAs participate in several metabolism-related pathways, evidencing their importance in DM. This systematic review suggests six lncRNAs are dysregulated in DM, constituting potential biomarkers of this disease.

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21 ◽  
Author(s):  
Y-h Taguchi

Background miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied.Methods Gene expression and promoter methylation profiles of 270 distinct human cell lines were obtained from Gene Expression Omnibus. P-values that describe both miRNA-targeted-gene promoter methylation and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Results Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. miRNA-targeted-gene promoter methylation may also be related to the seed region features of miRNA.Conclusions It was found that promoter methylation was correlated to miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation was especially enhanced in promoters of genes targeted by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs) and was suggested to be highly related to some seed region features of miRNAs.


F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21 ◽  
Author(s):  
Y-h Taguchi

Background miRNA regulation of target genes and promoter methylation are known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied. Methods Gene expression and promoter methylation profiles of 271 distinct human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeted-gene promoter methylaion and miRNA regulation of target genes were computed using the MiRaGE method proposed recently by the author.Results Significant changes in promoter methylation were associated with miRNA targeting. It was also found that miRNA-targeted-gene promoter hypomethylation was related to differential target gene expression; the genes with miRNA-targeted-gene promoter hypomethylation were downregulated during cell senescence and upregulated during cellular differentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs.Conclusions It was found that promoter methylation was affected by miRNA targeting. Furthermore, miRNA-targeted-gene promoter hypomethylation is suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).


F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 21
Author(s):  
Y-h Taguchi

Background miRNA regulation of target genes and promoter methylation were known to be the primary mechanisms underlying the epigenetic regulation of gene expression. However, how these two processes cooperatively regulate gene expression has not been extensively studied. Methods Gene expression and promoter methylation profiles of 271 distinct human cell lines were obtained from gene expression omnibus. P-values that describe both miRNA-targeting-specific promoter methylation and miRNA regulation of target genes were computed with the MiRaGE method proposed recently by the author. Results We found that promoter methylation was miRNA-targeting-specific. In other words, changes in promoter methylation were associated with miRNA binding at target genes. It was also found that miRNA-targeting-specific promoter hypomethylation was related to miRNA regulation; the genes with miRNA-targeting-specific promoter hypomethylation were downregulated during cell senescence and upregulated during cellulardierentiation. Promoter hypomethylation was especially enhanced for genes targeted by miR-548 miRNAs, which are non-conserved, and primate-specific miRNAs that are typically expressed at lower levels than the frequently investigated conserved miRNAs. Conclusions It was found that promoter methylation was affected by miRNA targeting. Furthermore, miRNA-targeting-specific promoter hypomethylation was suggested to facilitate gene regulation by miRNAs that are not strongly expressed (e.g., miR-548 miRNAs).


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoli Hu ◽  
Yang Liu ◽  
Zhitong Bing ◽  
Qian Ye ◽  
Chengcheng Li

Owing to metastases and drug resistance, the prognosis of breast cancer is still dismal. Therefore, it is necessary to find new prognostic markers to improve the efficacy of breast cancer treatment. Literature shows a controversy between moesin (MSN) expression and prognosis in breast cancer. Here, we aimed to conduct a systematic review and meta-analysis to evaluate the prognostic relationship between MSN and breast cancer. Literature retrieval was conducted in the following databases: PubMed, Web of Science, Embase, and Cochrane. Two reviewers independently performed the screening of studies and data extraction. The Gene Expression Omnibus (GEO) database including both breast cancer gene expression and follow-up datasets was selected to verify literature results. The R software was employed for the meta-analysis. A total of 9 articles with 3,039 patients and 16 datasets with 2,916 patients were ultimately included. Results indicated that there was a significant relationship between MSN and lymph node metastases (P < 0.05), and high MSN expression was associated with poor outcome of breast cancer patients (HR = 1.99; 95% CI 1.73–2.24). In summary, there is available evidence to support that high MSN expression has valuable importance for the poor prognosis in breast cancer patients.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-8-0039/.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chenlei Zheng ◽  
Cheng Wang ◽  
Tan Zhang ◽  
Ding Li ◽  
Xiao-feng Ni ◽  
...  

Objective. Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods. We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results. Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions. This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhi Chai ◽  
Yafei Lyu ◽  
Qiuyan Chen ◽  
Cheng-Hsin Wei ◽  
Lindsay Snyder ◽  
...  

Abstract Objectives To characterize and compare the impact of vitamin A (VA) deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways. Methods vitamin A deficient (VAD) mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. Total mRNA extracted from SI and colon were sequenced using Illumina HiSeq 2500 platform. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression patterns and co-expression patterns. Results The comparison between vitamin A sufficient (VAS) and VAD groups detected 49 and 94 DEGs in SI and colon, respectively. According to GO information, DEGs in the SI demonstrated significant enrichment in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, such as “humoral immune response” and “complement activation,” were positively associated with VA in SI. On the contrary, in colon, “cell division” was the only enriched category and was negatively associated with VA. WGCNA identified modules significantly correlated with VA status in SI and in colon. One of those modules contained five known retinoic acid targets. Therefore we have prioritized the other module members (e.g., Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) to be investigated as candidate genes regulated by VA. Comparison of co-expression modules between SI and colon indicated distinct VA effects on these two organs. Conclusions The results show that VA deficiency alters the gene expression profiles in SI and colon quite differently. Some immune-related genes (Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) may be novel targets under the control of VA in SI. Funding Sources NIH training grant and NIH research grant. Supporting Tables, Images and/or Graphs


2020 ◽  
Vol 18 (4) ◽  
pp. 357-370
Author(s):  
R. Viggers ◽  
Z. Al-Mashhadi ◽  
R. Fuglsang-Nielsen ◽  
S. Gregersen ◽  
J. Starup-Linde

2019 ◽  
Vol 35 (7) ◽  
pp. 1125-1140 ◽  
Author(s):  
Birce Dobrucalı

Purpose This paper aims to provide a comprehensive and systematic review of the extant empirical body of knowledge regarding the impact of Guanxi on international Business-to-Business (B-to-B) relationships. Design/methodology/approach After the collection and refinement of studies that appeared in marketing, business and management literature during 1995-2018 period, a systematic review was conducted to discover the current situation and future research directions on the subject. Findings Theoretically, vast majority of the reviewed studies lacked a theoretical foundation, with the remainder anchored primarily on the resource-based view, social network theory and social exchange theory. Methodologically, Ganqing, Xinren and Mianzi are the most frequently investigated dimensions, whereas Renqing is the least investigated dimension. Data are mostly obtained from both Chinese and Western counterparts through survey and analyzed through univariate and multivariate data analysis techniques. Empirically, extant research focused on many diverse outcomes including trust, financial performance, cooperation, satisfaction, time orientation, opportunism and liability of foreignness, while under-examining the drives of Guanxi. Research limitations/implications This study provides a synthesis of extant line of research on the subject that are published in peer-reviewed international journals, which publish research in English. A meta-analysis may be conducted for providing a further detailed framework. Originality/value This study contributes to international marketing literature by providing an in-depth and synthesized inventory of knowledge to scholars; deriving a comprehensive analysis of theoretical foundations, methodological approaches and findings addressed by scholars in the field; noticing theoretical, methodological and empirical gaps to be examined; and providing future research directions.


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