Expression Change Correlations Between Transposons and Their Adjacent Genes in Lung Cancers Reveal a Genomic Location Dependence and Highlights Cancer-Significant Genes

Arroyo, María Castellano; Larrosa, Rafael; Claros, M. Gonzalo; Bautista, Rocí­o

doi:10.1007/978-3-030-17938-0_8

Cited by 4 publications

(4 citation statements)

References 13 publications

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“…These are adjacent genes nearby a large ERV locus. Moreover, the coordinate dysregulation of HERVIP10F-int and SERINC2 has been previously reported in lung cancer (42), and derepression of HERVIP10F-int was also found in HCC1944 breast cancer cells compared with human mammary epithelial cell controls (48). Even the small number of tumors analyzed in our study implicates transposable element derepression driving altered expression of endogenous genes in human PanNETs.…”

Section: Discussionsupporting

confidence: 73%

“…ENCODE (Encyclopedia of DNA Elements) data showed that this region is marked by the repressive H3K9me3 heterochromatin mark in several cancer cell lines (41). A recent study in lung adenocarcinoma identified HERVIP10F-int and SERINC2 as a differentially expressed transposable element-gene pair, in which both the ERV and the adjacent gene were up-regulated (42). These data indicate the presence of coordinate regulation and the potential for HERVIP10F derepression to affect the expression of nearby genes, much like the example of IAP-d-int and Bgalp3 from our mouse data.…”

Section: Transcriptome Data From Human Pannets Supports Coordinate Dy...supporting

confidence: 75%

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Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo

Sun

Moyer

et al. 2020

Sci. Adv.

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Tumor sequencing studies have emphasized the role of epigenetics and altered chromatin homeostasis in cancer. Mutations in DAXX, which encodes a chaperone for the histone 3.3 variant, occur in 25% of pancreatic neuroendocrine tumors (PanNETs). To advance our understanding of physiological functions of Daxx, we developed a conditional Daxx allele in mice. We demonstrate that Daxx loss is well tolerated in the pancreas but creates a permissive transcriptional state that cooperates with environmental stress (inflammation) and other genetic lesions (Men1 loss) to alter gene expression and cell state, impairing pancreas recovery from inflammatory stress in vivo. The transcriptional changes are associated with dysregulation of endogenous retroviral elements (ERVs), and dysregulation of endogenous genes near ERVs is also observed in human PanNETs with DAXX mutations. Our results reveal a physiologic function of DAXX, provide a mechanism associated with impaired tissue regeneration and tumorigenesis, and expand our understanding of ERV regulation in somatic cells.

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Section: Discussionsupporting

confidence: 73%

Section: Transcriptome Data From Human Pannets Supports Coordinate Dy...supporting

confidence: 75%

Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo

Sun

Moyer

et al. 2020

Sci. Adv.

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“…CHRD was found to be significantly under-expressed in ovarian cancer compared to normal tissues suggesting its potential of regulating BMP activity in normal ovarian surface epithelium physiology [82]. Several reports on IL1RL1 down-regulation in lung cancer also validates our findings in this study [83,84]. Here, our findings validate the co-expression significance of BMP5 with its predicted functional protein partners in several cancers.…”

Section: Discussionsupporting

confidence: 88%

A Multi-Omics Analysis of Bone Morphogenetic Protein 5 (BMP5) mRNA Expression and Clinical Prognostic Outcomes in Different Cancers Using Bioinformatics Approaches

Karim¹,

Samad²,

Adhikari

et al. 2020

Biomedicines

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Cumulative studies have provided controversial evidence for the prognostic values of bone morphogenetic protein 5 (BMP5) in different types of cancers such as colon, breast, lung, bladder, and ovarian cancer. To address the inconsistent correlation of BMP5 expression with patient survival and molecular function of BMP5 in relation to cancer progression, we performed a systematic study to determine whether BMP5 could be used as a prognostic marker in human cancers. BMP5 expression and prognostic values were assessed using different bioinformatics tools such as ONCOMINE, GENT, TCGA, GEPIA, UALCAN, PrognoScan, PROGgene V2 server, and Kaplan–Meier Plotter. In addition, we used cBioPortal database for the identification and analysis of BMP5 mutations, copy number alterations, altered expression, and protein–protein interaction (PPI). We found that BMP5 is frequently down-regulated in our queried cancer types. Use of prognostic analysis showed negative association of BMP5 down-regulation with four types of cancer except for ovarian cancer. The highest mutation was found in the R321*/Q amino acid of BMP5 corresponding to colorectal and breast cancer whereas the alteration frequency was higher in lung squamous carcinoma datasets (>4%). In PPI analysis, we found 31 protein partners of BMP5, among which 11 showed significant co-expression (p-value < 0.001, log odds ratio > 1). Pathway analysis of differentially co-expressed genes with BMP5 in breast, lung, colon, bladder and ovarian cancers revealed the BMP5-correlated pathways. Collectively, this data-driven study demonstrates the correlation of BMP5 expression with patient survival and identifies the involvement of BMP5 pathways that may serve as targets of a novel biomarker for various types of cancers in human.

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“…Among the up-regulated genes, 13% of which are characterized by intragenic ERVs, two genes were found to be significantly up-regulated in DAXX mutant tumors: FABP3 (Fatty-acid-binding protein 3) and Serine incorporator 2 ( SERINC2), neighboring genes close to an ERV locus. The dysregulation of SERINC2 and the nearby ERV have just been described in human lung adenocarcinoma also [ 86 ].…”

Section: Permissive Chromatin Landscapementioning

confidence: 99%

Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms

Pastorino

Grillo

Albertelli

et al. 2021

IJMS

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Genomic studies have identified some of the most relevant genetic players in Neuroendocrine Neoplasm (NEN) tumorigenesis. However, we are still far from being able to draw a model that encompasses their heterogeneity, elucidates the different biological effects consequent to the identified molecular events, or incorporates extensive knowledge of molecular biomarkers and therapeutic targets. Here, we reviewed recent insights in NEN tumorigenesis from selected basic research studies on animal models, highlighting novel players in the intergenic cooperation and peculiar mechanisms including splicing dysregulation, chromatin stability, or cell dedifferentiation. Furthermore, models of tumorigenesis based on composite interactions other than a linear progression of events are proposed, exemplified by the involvement in NEN tumorigenesis of genes regulating complex functions, such as MEN1 or DAXX. Although limited by interspecies differences, animal models have proved helpful for the more in-depth study of every facet of tumorigenesis, showing that the identification of driver mutations is only one of the many necessary steps and that other mechanisms are worth investigating.

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Expression Change Correlations Between Transposons and Their Adjacent Genes in Lung Cancers Reveal a Genomic Location Dependence and Highlights Cancer-Significant Genes

Cited by 4 publications

References 13 publications

Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo

Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo

A Multi-Omics Analysis of Bone Morphogenetic Protein 5 (BMP5) mRNA Expression and Clinical Prognostic Outcomes in Different Cancers Using Bioinformatics Approaches

Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms

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