Dataset Information

Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS).

ABSTRACT: Transient receptor potential melastatins (TRPMs) are most well known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet, the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of >1,300 TRPM-like sequences from 14 phyla (Annelida, Arthropoda, Brachiopoda, Chordata, Cnidaria, Echinodermata, Hemichordata, Mollusca, Nematoda, Nemertea, Phoronida, Priapulida, Tardigrada, and Xenacoelomorpha), including sequences from a variety of recently sequenced genomes that fill what would otherwise be substantial taxonomic gaps. These findings suggest: 1) the previously recognized TRPM family is in fact two distinct families, including canonical TRPM channels and an eighth major previously undescribed family of animal TRP channel, TRP soromelastatin; 2) two TRPM clades predate the last bilaterian-cnidarian ancestor; and 3) the vertebrate-centric trend of categorizing TRPM channels as 1-8 is inappropriate for most phyla, including other chordates.

SUBMITTER: Himmel NJ

PROVIDER: S-EPMC7306681 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS).

Himmel Nathaniel J NJ Gray Thomas R TR Cox Daniel N DN

Molecular biology and evolution 20200701 7

Transient receptor potential melastatins (TRPMs) are most well known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet, the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of >1,300 TRPM-like sequences from 14 phyla (Annel ...[more]

PMID: 32159767

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Project description:BackgroundTransient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood.MethodsPublic databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs.ResultsInitially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRT-PCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis.ConclusionTRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma.

Dataset Information

Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS).

Publications

Phylogenetics Identifies Two Eumetazoan TRPM Clades and an Eighth TRP Family, TRP Soromelastatin (TRPS).

Similar Datasets

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