WikiPathways: connecting communities

Martens, Marvin; Ammar, Ammar; Riutta, Anders; Waagmeester, Andra; Slenter, Denise; Hanspers, Kristina; Miller, Ryan; Digles, Daniela; Lopes, Élisson Nogueira; Ehrhart, Friederike; Dupuis, Lauren J.; Winckers, Laurent; Coort, Susan L.; Willighagen, Egon; Evelo, Chris T.; Pico, Alexander; Kutmon, Martina

doi:10.1093/nar/gkaa1024

Cited by 669 publications

(584 citation statements)

References 51 publications

Supporting

Mentioning

502

Contrasting

Unclassified

Order By: Relevance

“…Given the regulatory role of the actin cytoskeleton in YAP/TAZ modulation, we wondered whether the observed alterations in YAP/TAZ phosphorylation status mediated by miR-582-5p could be explained by altered cytoskeletal dynamics. To investigate this, we first obtained a list of predicted miR-582-5p targets from TargetScan [22] and overlapped them with a list of genes involved in regulating actin cytoskeleton (sourced from Wikipathways) [38]. This yielded nine common genes as candidate targets of miR-582-5p ( Figure 4A).…”

Section: Mir-582-5p Suppresses Hippo-yap/taz Signaling By Targeting Amentioning

confidence: 99%

“…TargetScan was utilized to gather the predicted targets of hsa-miR-582-5p and to delineate the potential binding sites of hsa-miR-582-5p on the 3'UTR of NCKAP1 and PIP5K1C [22]. Wikipathways was used to compile the list of genes involved in the regulation of actin cytoskeleton [38]. RNAhybrid was employed to predict the minimum free energy [39] of miR-582-5p binding on sites present in 3'UTRs of NCKAP1, PIP5K1C, and NOTCH1.…”

Section: Database Analysismentioning

confidence: 99%

See 1 more Smart Citation

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer

Zhu

Mitheera

Finch-Edmondson

et al. 2021

Cancers

View full text Add to dashboard Cite

The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally. Amongst the cancer-relevant microRNAs, miR-582-5p suppresses cell growth and tumorigenesis by inhibiting the expression of oncogenes, including AKT3, MAP3K2 and NOTCH1. Given the oncogenic role of YAP/TAZ in solid tumors, we scrutinized the possible interplay between miR-582-5p and Hippo-YAP/TAZ signaling. Correlation analysis in NSCLC cells revealed a positive relationship between the expression of mature miR-582-5p and the proportion of phosphorylated YAP/TAZ. Intriguingly, YAP/TAZ knockdown reduced the expression of mature miR-582-5p but increased that of primary miR-582. Overexpression of miR-582-5p resulted in increased phosphorylation of YAP/TAZ with a concomitant reduction in cell proliferation and enhanced apoptosis. Mechanistically, we find that miR-582-5p targets actin regulators NCKAP1 and PIP5K1C, which may be responsible for the observed alteration in F-actin, known to modulate YAP/TAZ. We postulate that regulation of the actin cytoskeleton by miR-582-5p may attenuate YAP/TAZ activity. Altogether, this study reveals a novel mechanism of YAP/TAZ regulation by miR-582-5p in a cytoskeleton-dependent manner and suggests a negative feedback loop, highlighting the therapeutic potential of restoring miR-582-5p expression in treating NSCLC.

show abstract

Section: Mir-582-5p Suppresses Hippo-yap/taz Signaling By Targeting Amentioning

confidence: 99%

Section: Database Analysismentioning

confidence: 99%

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer

Zhu

Mitheera

Finch-Edmondson

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…To that end, we performed differential expression between enterocytes in which LINE-1 was detected and those where it was not. We then performed GSEA 18 using Reactome 19 , PID 20 , WikiPathways 21 , KEGG 22 and BioCarta 23 gene sets. At FDR < 5%, this yielded 28 significantly enriched gene sets (full list in table S1).…”

Section: Resultsmentioning

confidence: 99%

LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq

McKerrow

Evans

Rocha

et al. 2021

Preprint

View full text Add to dashboard Cite

LINE-1 retrotransposons are known to be expressed in early development, in tumors and in the germline. Less is known about LINE-1 expression at the single cell level, especially outside the context of cancer. Because LINE-1 elements are present at a high copy number, many transcripts that are not driven by the LINE-1 promoter nevertheless terminate at the LINE-1 3’ UTR. Thus, 3’ targeted single cell RNA-seq datasets are not appropriate for studying LINE-1. However, 5’ targeted single cell datasets provide an opportunity to analyze LINE-1 expression at the single cell level. Most LINE-1 copies are 5’ truncated, and a transcript that contains the LINE-1 5’ UTR as its 5’ end is likely to have been transcribed from its promoter. We developed a method, L1-sc (LINE-1 expression for single cells), to quantify LINE-1 expression in 5’ targeted 10x genomics single cell RNA-seq datasets. Our method confirms that LINE-1 expression is high in cancer cells, but low or absent from immune cells. We also find that LINE-1 expression is elevated in epithelial compared to immune cells outside of the context of cancer and that it is also elevated in neurons compared to glia in the mouse hippocampus.

show abstract

“…A number of papers cover metabolic pathways. WikiPathways ( 37 ) reports increased numbers of pathways, metabolites and—importantly, given its modus operandi—contributors. Distinct portals with their own URLs support communities focused on topics as diverse as COVID-19, rare diseases and lipid metabolism.…”

Section: New and Updated Databasesmentioning

confidence: 99%

The 2021 Nucleic Acids Research database issue and the online molecular biology database collection

Rigden

Fernández

2020

Nucleic Acids Research

View full text Add to dashboard Cite

The 2021 Nucleic Acids Research database Issue contains 189 papers spanning a wide range of biological fields and investigation. It includes 89 papers reporting on new databases and 90 covering recent changes to resources previously published in the Issue. A further ten are updates on databases most recently published elsewhere. Seven new databases focus on COVID-19 and SARS-CoV-2 and many others offer resources for studying the virus. Major returning nucleic acid databases include NONCODE, Rfam and RNAcentral. Protein family and domain databases include COG, Pfam, SMART and Panther. Protein structures are covered by RCSB PDB and dispersed proteins by PED and MobiDB. In metabolism and signalling, STRING, KEGG and WikiPathways are featured, along with returning KLIFS and new DKK and KinaseMD, all focused on kinases. IMG/M and IMG/VR update in the microbial and viral genome resources section, while human and model organism genomics resources include Flybase, Ensembl and UCSC Genome Browser. Cancer studies are covered by updates from canSAR and PINA, as well as newcomers CNCdatabase and Oncovar for cancer drivers. Plant comparative genomics is catered for by updates from Gramene and GreenPhylDB. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been substantially updated, revisiting nearly 1000 entries, adding 90 new resources and eliminating 86 obsolete databases, bringing the current total to 1641 databases. It is available at https://www.oxfordjournals.org/nar/database/c/.

show abstract

WikiPathways: connecting communities

Cited by 669 publications

References 51 publications

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer

LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq

The 2021 Nucleic Acids Research database issue and the online molecular biology database collection

Contact Info

Product

Resources

About