The Emerging Concept of Transportome: State of the Art.

The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life. Today, thanks to the high-throughput technologies of the postgenomic era, the omics approach to the study of the transportome is becoming increasingly popular in different areas of biomedical research, allowing for a more comprehensive, integrated, and functional perspective of this complex cellular apparatus. This article represents a first effort for a systematic review of the scientific literature on this topic. Here we provide a brief overview of all those studies, both primary and meta-analyses, that looked at the transportome as a whole, regardless of the biological problem or the models they used. A subsequent section is devoted to the methodological aspect by reviewing the most important public databases annotating ion channels and transporters, along with the tools they provide to retrieve such information. Before conclusions, limitations and future perspectives are also discussed.

Corrigendum to "Transcriptomic data of Bevacizumab-adapted colorectal adenocarcinoma cells HCT-116" [Data In Brief, Volume 48, (Available online 17 March 2023) 1-9/Article 109069].

[This corrects the article DOI: 10.1016/j.dib.2023.109069.].

BioTEA: Containerized Methods of Analysis for Microarray-Based Transcriptomics Data.

Tens of thousands of gene expression data sets describing a variety of model organisms in many different pathophysiological conditions are currently stored in publicly available databases such as the Gene Expression Omnibus (GEO) and ArrayExpress (AE). As microarray technology is giving way to RNA-seq, it becomes strategic to develop high-level tools of analysis to preserve access to this huge amount of information through the most sophisticated methods of data preparation and processing developed over the years, while ensuring, at the same time, the reproducibility of the results. To meet this need, here we present bioTEA (biological Transcript Expression Analyzer), a novel software tool that combines ease of use with the versatility and power of an R/Bioconductor-based differential expression analysis, starting from raw data retrieval and preparation to gene annotation. BioTEA is an R-coded pipeline, wrapped in a Python-based command line interface and containerized with Docker technology. The user can choose among multiple options-including gene filtering, batch effect handling, sample pairing, statistical test type-to adapt the algorithm flow to the structure of the particular data set. All these options are saved in a single text file, which can be easily shared between different laboratories to deterministically reproduce the results. In addition, a detailed log file provides accurate information about each step of the analysis. Overall, these features make bioTEA an invaluable tool for both bioinformaticians and wet-lab biologists interested in transcriptomics. BioTEA is free and open-source.

The Transcriptional Landscape of BRAF Wild Type Metastatic Melanoma: A Pilot Study.

Melanoma is a relatively rare disease worldwide; nevertheless, it has a great relevance in some countries, such as in Europe. In order to shed some light upon the transcriptional profile of skin melanoma, we compared the gene expression of six independent tumours (all progressed towards metastatic disease and with wild type BRAF) to the expression profile of non-dysplastic melanocytes (considered as a healthy control) in a pilot study. Paraffin-embedded samples were manually micro-dissected to obtain enriched samples, and then, RNA was extracted and analysed through a microarray-based approach. An exhaustive bioinformatics analysis was performed to identify differentially expressed transcripts between the two groups, as well as enriched functional terms. Overall, 50 up- and 19 downregulated transcripts were found to be significantly changed in the tumour compared to the control tissue. Among the upregulated transcripts, the majority belonged to the immune response group and to the proteasome, while most of the downregulated genes were related to cytosolic ribosomes. A Gene Set Enrichment Analysis (GSEA), along with the RNA-Seq data retrieved from the TCGA/GTEx databases, confirmed the general trend of downregulation affecting cytoribosome proteins. In contrast, transcripts coding for mitoribosome proteins showed the opposite trend.

TRPM8-Rap1A Interaction Sites as Critical Determinants for Adhesion and Migration of Prostate and Other Epithelial Cancer Cells.

Emerging evidence indicates that the TRPM8 channel plays an important role in prostate cancer (PCa) progression, by impairing the motility of these cancer cells. Here, we reveal a novel facet of PCa motility control via direct protein-protein interaction (PPI) of the channel with the small GTPase Rap1A. The functional interaction of the two proteins was assessed by active Rap1 pull-down assays and live-cell imaging experiments. Molecular modeling analysis allowed the identification of four putative residues involved in TRPM8-Rap1A interaction. Point mutations of these sites impaired PPI as shown by GST-pull-down, co-immunoprecipitation, and PLA experiments and revealed their key functional role in the adhesion and migration of PC3 prostate cancer cells. More precisely, TRPM8 inhibits cell migration and adhesion by trapping Rap1A in its GDP-bound inactive form, thus preventing its activation at the plasma membrane. In particular, residues E207 and Y240 in the sequence of TRPM8 and Y32 in that of Rap1A are critical for the interaction between the two proteins not only in PC3 cells but also in cervical (HeLa) and breast (MCF-7) cancer cells. This study deepens our knowledge of the mechanism through which TRPM8 would exert a protective role in cancer progression and provides new insights into the possible use of TRPM8 as a new therapeutic target in cancer treatment.