LNCRNA ISOFORMS CONCURRENTLY MODULATED BY METFORMIN IN MULTIPLE HUMAN CELL LINES

Published in 26/04/2022 - ISBN: 978-65-5941-645-5

Paper Title
LNCRNA ISOFORMS CONCURRENTLY MODULATED BY METFORMIN IN MULTIPLE HUMAN CELL LINES
Authors
  • Izabela Mamede
  • Lucio Rezende Queiroz
  • Ana Gabrielle Batista de Melo
  • Thomaz Luscher Dias
  • Marcelo Rizzatti Luizon
  • Glória Regina Franco
Modality
Xpress presentation
Subject area
Omics
Publishing Date
26/04/2022
Country of Publishing
Brasil
Language of Publishing
Inglês
Paper Page
https://www.even3.com.br/anais/xmeetingxp2021/409898-lncrna-isoforms-concurrently-modulated-by-metformin-in-multiple-human-cell-lines
ISBN
978-65-5941-645-5
Keywords
lncRNA, isoforms, metformin, transcriptomics, RNA-seq
Summary
Long non-coding RNAs (lncRNAs) are central regulators of several cellular processes and are able to fine-tune the expression of other genes, by acting in transcription, translation, and even guiding epigenetic modifications. lncRNAs undergo splicing and have multiple transcribed isoforms, on average twice as many isoforms as protein-coding genes. Nevertheless, lncRNAs expression are routinely analyzed only at gene level. Metformin is the drug used as first-line oral therapy for type II Diabetes and has also been proposed as treatment for several other diseases, including various types of cancer. Metformin acts as a homeostasis regulator, controlling cell proliferation and influencing the cell epigenome. However, its mechanism of action remains poorly elucidated, and its potent anti-aging and anti-carcinogenic effects are commonly seen, but not thoroughly explained. Here we evaluated all publicly available RNA-seq datasets in which different cells were treated with metformin, selecting those with higher depth, read length, and which were stranded and paired-end. Those features allowed us to do a statistically comparable analysis between multiple cell types and metformin concentrations in treated and untreated conditions. We sought differentially expressed lncRNA isoforms and used comparable tumor datasets to infer the biological effects of the isoforms. Sequence pseudo-alignment was performed with Salmon (v.1.5.0) using GENCODE human annotation v37, quality check with FastQC, and differential expression was done with DESeq2 and Fishpond. Functional enrichment was done with lncRNA2Pathways and integrated between all series. Pathways with FDR <0.05 were kept in the analysis. Count correlation and co-expression analysis were done in several R packages including WGCNA. Transcript annotation was performed on Ensembl and UCSC genome browsers. Enrichment analysis showed multiple pathways in common between all analyzed experiments associated with lncRNA which were over and under-expressed. These lncRNA may be central to metformin action in altered pathways in cancer, such as signaling by EGFR, FGFR, and ERBBs. Also, there were lncRNA isoforms involved in key metformin pathways as reduction of cAMP levels and respiratory electron transport. We found 36 lncRNA isoforms modulated in at least four metformin experiments. Among the lncRNA genes that give rise to these isoforms, several are also related to cancer, as NEAT1, MALAT1, and GAS5. We found a recently annotated transcript, AC125807.2-201, that is downregulated in metformin-treated cells and upregulated gastric, rectal, and hepatic cancer. Further analysis showed that the genomic locus of this lncRNA overlaps with a CTCF-binding mark on chromosome 6, which points to a potential 3D chromatin structure regulatory role of this lncRNA and its action as a topological anchor point RNA (tap-RNA). Our results provide evidence that Metformin regulates the expression of key lncRNA isoforms, and we argue these isoforms have active roles in metformin known and proposed effects.
Title of the Event
X-Meeting XPerience 2021
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital
DOI
LinkGet DOI

How to cite

MAMEDE, Izabela et al.. LNCRNA ISOFORMS CONCURRENTLY MODULATED BY METFORMIN IN MULTIPLE HUMAN CELL LINES.. In: X-Meeting presentations. Anais...São Paulo(SP) AB3C, 2021. Available in: https//www.even3.com.br/anais/xmeetingxp2021/409898-LNCRNA-ISOFORMS-CONCURRENTLY-MODULATED-BY-METFORMIN-IN-MULTIPLE-HUMAN-CELL-LINES. Access in: 13/06/2024

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