Overexpression of transposable elements is associated with immune evasion and poor outcome in colorectal cancer

Zhu, Xiaoqiang; Hu, Fang; Gladysz, Kornelia; Barbour, Jayne A.; Wong, Jason

doi:10.1016/j.ejca.2021.08.003

Cited by 18 publications

(14 citation statements)

References 55 publications

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“…L1HS and L1PA*) are overexpressed in cancer cells only (figure 3d), hinting to a possible de-repression of such young insertions in cancer conditions. As a validation to our differential analysis, we checked the presence of 16 TE features known to be overexpressed in CRC from bulk RNA-seq studies (52, 53), and confirmed the presence of 10 out of 16 CRC TE markers among the TE subfamilies belonging to our cancer TE signature (figure 3e). Furthermore, thanks to the single-cell resolution, we were able to reveal a previously uncharacterized heterogeneous distribution of CRC TE markers (figure 3f).…”

Section: Resultsmentioning

confidence: 59%

IRescue: uncertainty-aware quantification of transposable elements expression at single cell level

Polimeni

Marasca

Ranzani

et al. 2022

Preprint

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Transposable elements (TEs) are interspersed and repetitive DNA sequences that contribute to the evolution of species by introducing novel regulatory sequences in the eukaryotic genome, and their transcription have been associated to both physiological functions and detrimental effects in human cells. Given their ubiquity and redundancy, the transcriptome analysis of TEs is notoriously challenging and requires specialized tools. While a plethora of software is available for bulk RNA-Seq, few attempts have been made for measuring the expression of TEs in scRNA-seq data so far. Here, we present IRescue (Interspersed Repeats single-cell quantifier), a software to quantify TE expression in scRNA-seq using a UMI deduplication algorithm to solve the allocation of reads ambiguously mapped on interspersed TEs. Using simulated data, we demonstrate that IRescue is precise at estimating the expression of TE subfamilies. Furthermore, by analysing normal and cancer cells from colorectal cancer (CRC) patients, we identify the TE expression signature of CRC cells, where we found young LINE1 elements to be specifically enriched in subpopulations of cancer cells, compared to normal cells. Finally, we show the heterogeneity and expression dynamics of CRC TE markers previously characterized at bulk-level only, and that the expression of such markers is the result of the transcription of tumor-specific alternative isoforms of human oncogenes. With IRescue, we long to enable adding the layer of TE expression in the multimodal analysis of single cell sequencing and to facilitate the discovery of novel markers from the high and increasing amount of scRNA-seq experiments data.

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Section: Resultsmentioning

confidence: 59%

IRescue: uncertainty-aware quantification of transposable elements expression at single cell level

Polimeni

Marasca

Ranzani

et al. 2022

Preprint

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“…These results suggest that high PPP1R3G expression correlates with immune infiltration in the tumor microenvironment, which itself correlates with the prognosis of small cell lung cancer [ 28 ]. The subset of patients with colorectal cancer with high immune infiltration have a poor prognosis; Their tumors had high levels of T cell infiltration and also showed increased expression of programmed death ligand 1 [ 29 ]. Although several studies have supported the point that immune cell infiltration leads to a poor prognosis, whether our results of our study are consistent with them requires further study.…”

Section: Discussionmentioning

confidence: 99%

Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) correlates with poor prognosis and immune infiltration in lung adenocarcinoma

et al. 2021

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The protein phosphatase 1 regulatory subunit 3G (PPP1R3G) participates in many tumor biological processes; however, its effects on lung adenocarcinoma (LUAD) have not been clarified. Therefore, this study aimed to explore the correlation between PPP1R3G and the prognosis and immune invasion of LUAD. We evaluated the relationship between PPP1R3G and LUAD using a wide range of databases and analysis tools, including UALCAN, TIMER, miRDB, The Human Protein Atlas and the MethSurv database. First, we explored the mRNA and protein expression levels of PPP1R3G in LUAD, and results were validated using real-time PCR. Next, we explored the relationship between PPP1R3G expression and clinical features. Finally, Kaplan-Meier curves and Cox regression were employed to investigate the prognostic significance of PPP1R3G in LUAD. In addition, we explored the relationship between the expression of PPP1R3G and immune infiltration using the TIMER database. We analyzed the relationship between PPP1R3G and methylation using MethSurv database. Results showed that PPP1R3G expression in LUAD tissues was higher than that in normal tissues, and high expression was suggestive of a poor prognosis. Moreover, PPP1R3G expression was positively correlated with the immune infiltration of CD4+ T cells, macrophages, neutrophils, and dendritic cells. PPP1R3G copy number variations also demonstrated remarkable associations with the levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Finally, a PPP1R3G-associated regulatory network was constructed. Overall, PPP1R3G might be a poor prognostic biomarker for LUAD and is associated with tumor immune cell infiltration.

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“…The results highlighted a specific upregulation of a LINE and an LTR element in malignant melanomas of transgenic fish. Although this has to be confirmed, TEs expression and methylation levels could be used as prognostic markers [ 50 , 51 ]. Indeed, the quantification of Alu sequence and of LINE-1 methylation may distinguish lung or breast cancer patients from healthy patients [ 50 ].…”

Section: Involvement Of Tes In Human Cancersmentioning

confidence: 99%

“…This study also showcases that three of the 34 patients analyzed for event-free survival had more than 100 TE insertions, suggesting that the greater the number of TE insertions, the longer the event-free survival time [ 34 ]. Finally, in colorectal cancer patients, the expression level of some TEs, i.e., nine among SVA, SINE, LINE and HERV families, was correlated with decreased survival [ 51 ]. In addition, tumors with the highest TE expression level showed increased immune cell infiltration with upregulation of interferon signaling pathways and increased expression of PD-L1 in immune cells [ 51 ].…”

Section: Involvement Of Tes In Human Cancersmentioning

confidence: 99%

“…Finally, in colorectal cancer patients, the expression level of some TEs, i.e., nine among SVA, SINE, LINE and HERV families, was correlated with decreased survival [ 51 ]. In addition, tumors with the highest TE expression level showed increased immune cell infiltration with upregulation of interferon signaling pathways and increased expression of PD-L1 in immune cells [ 51 ].…”

Section: Involvement Of Tes In Human Cancersmentioning

confidence: 99%

See 1 more Smart Citation

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

Chénais

2022

IJMS

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Transposable elements (TEs) are recognized as major players in genome plasticity and evolution. The high abundance of TEs in the human genome, especially the Alu and Long Interspersed Nuclear Element-1 (LINE-1) repeats, makes them responsible for the molecular origin of several diseases. This involves several molecular mechanisms that are presented in this review: insertional mutation, DNA recombination and chromosomal rearrangements, modification of gene expression, as well as alteration of epigenetic regulations. This literature review also presents some of the more recent and/or more classical examples of human diseases in which TEs are involved. Whether through insertion of LINE-1 or Alu elements that cause chromosomal rearrangements, or through epigenetic modifications, TEs are widely implicated in the origin of human cancers. Many other human diseases can have a molecular origin in TE-mediated chromosomal recombination or alteration of gene structure and/or expression. These diseases are very diverse and include hemoglobinopathies, metabolic and neurological diseases, and common diseases. Moreover, TEs can also have an impact on aging. Finally, the exposure of individuals to stresses and environmental contaminants seems to have a non-negligible impact on the epigenetic derepression and mobility of TEs, which can lead to the development of diseases. Thus, improving our knowledge of TEs may lead to new potential diagnostic markers of diseases.

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Overexpression of transposable elements is associated with immune evasion and poor outcome in colorectal cancer

Cited by 18 publications

References 55 publications

IRescue: uncertainty-aware quantification of transposable elements expression at single cell level

IRescue: uncertainty-aware quantification of transposable elements expression at single cell level

Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) correlates with poor prognosis and immune infiltration in lung adenocarcinoma

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

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