TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease

Masood, Motasim; Grimm, Stefan; El‐Bahrawy, Mona; Yagüe, Ernesto

doi:10.3390/cancers12123862

Cited by 14 publications

(12 citation statements)

References 66 publications

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“…From RNA-Seq results, 10 FRGs were identi ed as the hub genes via overlapping 295 DEGs. TMEFF2, a type I transmembrane protein with an EGF-like and two follistatin motifs 2 proteins, was selectively expressed in the brain and prostate [20]. Based on our analysis, TMEFF2 was a co-expressed gene and correlated with GPX4 and SLC7A11, as determined by GeneMANIA and GEPIA.…”

Section: Discussionmentioning

confidence: 62%

Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure

Huang

Jiang

et al. 2023

Preprint

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Few studies are focusing on the mechanism of erastin acts on prostate cancer(PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. In the current study, in vitro assays were performed to evaluate the ferroptotic levels of PCa cells under erastin treatment. RNA-sequecing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways, modules, transcription factors, and expression levels of DEGs. Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentration of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were screened and identified in two cells under erastin exposure and significantly enriched for association with several pathways, including DNA replication, steroid hormone biosynthesis, and cell cycle, et al. For four hub FRGs, TMEFF2 in PCa tissue is higher than in normal tissue and the expression levels of CLU, NRXN3, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in LNCaP cells but not in PC3 cells. The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP cells. This study extends our understanding of the molecular mechanism in erastin-affected PCa cells, and provides potential treatment ideas for PCa therapy.

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Section: Discussionmentioning

confidence: 62%

Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure

Huang

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…From RNA-Seq results, 10 genes including CLU, IL1B, MET, NRXN3, PLXNA4, GAD1, UNC5B, SLC7A5, DAPK1, and TMEFF2 were identified as the hub genes via overlapping 295 DEGs. TMEFF2, a type I transmembrane protein with an EGF-like and two follistatin motifs 2 proteins, was selectively expressed in the brain and prostate [21]. Based on our analysis, TMEFF2 was a co-expressed gene and correlated with GPX4 and SLC7A11, as determined by GeneMANIA and GEPIA.…”

Section: Discussionmentioning

confidence: 62%

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

Huang

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

Few studies are focusing on the mechanism of erastin acts on prostate cancer(PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa treatment targets are rarely known. In the current study, in vitro assays were performed to evaluate the ferroptotic levels of PCa cells under erastin treatment. RNA-seq was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways, module, transcription factors, and expression levels of DEGs. Erastin inhibited the expression of ferroptosis marker SLC7A11 and cell survivability in both PCa cells. After treatment with erastin, the concentration level of MDA and Fe2+ significantly increased, whereas GSH and GSSG significantly decreased in PCa cells. A total of 295 overlapping DEGs were screened and identified in two cells under erastin exposure and significantly enriched for association with some pathways. The expression levels of four hub FRGs, including TMEFF2, CLU, NRXN3, and UNC5B, were significantly different in PCa and normal tissues. TMEFF2 was the gene co-expressed with SLC7A11 and GPX4. In both PCa cells, the expression levels of SLC7A11 and cell growth were inhibited after the knockdown of TMEFF2. The concentration of Fe2+ significantly increased in two TMEFF2 downregulated cells. In conclusion, FRGs and their correlations with ferroptosis in PCa were identified and validated. Our results showed that these FRGs play a crucial role in PCa, and offered the potential therapeutic target genes for the investigation and treatment of PCa.

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“…We, therefore, decided to explore the functional features that varied among coDIU genes that had isoforms in the Pvalb expression cluster. Remarkably, two of the detected coDIU genes were membrane-associated proteoglycans Gpc1 and Tmeff2, which have been described to have neuronal function in previous studies 74,75 . These genes presented coordinated switches in isoform expression in the Pvalb (cluster 1) and Scng (cluster2) subtypes (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 72%

acorde unravels functionally interpretable networks of isoform co-usage from single cell data

et al. 2022

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Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may be relevant in cellular function has not been explored yet. Here, we present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we develop and validate percentile correlations, an innovative approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next, acorde uses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs, and domains potentially controlled by the coordination of post-transcriptional regulation. The code for acorde is available at https://github.com/ConesaLab/acorde.

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TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease

Cited by 14 publications

References 66 publications

Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure

Identification of ferroptosis related genes and pathways in prostate cancer cells under erastin exposure

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

acorde unravels functionally interpretable networks of isoform co-usage from single cell data

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