Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers

Wallace, Tiffany A.; Downey, Rónán; Seufert, Caleb; Schetter, Aaron J.; Dorsey, Tiffany H.; Johnson, Carol; Goldman, Radoslav; Loffredo, Christopher A.; Yan, Peisha; Sullivan, Frank; Giles, Francis J.; Wang-Johanning, Feng; Ambs, Stefan; Glynn, Sharon A.

doi:10.1093/carcin/bgu114

Cited by 77 publications

(86 citation statements)

References 49 publications

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“…We have previously shown that ERV activity has been suppressed by body size throughout evolution, probably due to higher cancer burden [21], and so increased HERV expression could be detrimental. For example, increased HERV-K expression was detected in germ cell and trophoblastic tumours [17], melanoma cells [27], as well as in the blood of breast cancer [32] and prostate cancer patients [31]. However, whether the expression of HERVs drive tumorigenesis or are the result of the aberrant gene expression in cancers is still undetermined [11].…”

Section: Discussionmentioning

confidence: 99%

Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency

et al. 2016

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Background: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. Results:In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. Conclusions:We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies.

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Section: Discussionmentioning

confidence: 99%

Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency

et al. 2016

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“…Serum proviral mRNA levels tended to be higher in the patients who later on developed the metastatic disease [207]. Aberrant overexpression of HERV-K/HML-2 (ERVK) proviruses was found also in prostate cancer [208] and HERV-K/HML-2 (ERVK) encoded transcripts or proteins are considered as possible biomarkers of malignization, being overexpressed for the patients with poor prognosis [209]. Increased HERV-K/ HML-2 (ERVK) Env gene expression was detected in the prostate tumors in 40 % of European-American and 61 % of African-American patients [208].…”

Section: Cancermentioning

confidence: 99%

“…Aberrant overexpression of HERV-K/HML-2 (ERVK) proviruses was found also in prostate cancer [208] and HERV-K/HML-2 (ERVK) encoded transcripts or proteins are considered as possible biomarkers of malignization, being overexpressed for the patients with poor prognosis [209]. Increased HERV-K/ HML-2 (ERVK) Env gene expression was detected in the prostate tumors in 40 % of European-American and 61 % of African-American patients [208]. Expression of some individual HERV-K/HML-2 (ERVK) elements can be of an outstanding importance to follow prostate cancer development, as recently shown for the HERV-K/HML-2 (ERVK) (ch22q11.23) Gag gene [209].…”

Section: Cancermentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

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Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

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“…[91][92][93][94][95][96][97] Nevertheless, characteristic patterns of HERVs expression are often seen in various tumors and can be considered as possible biomarkers of malignization, offering a unique approach to immunotherapy. 58 The major contribution of HERV sequences to the evolution of the species presumably depends on their LTRs that can trigger chromosomal breaks through recombination events and serve as natural or alternative promoters/enhancers, capable of modulating transcription.…”

Section: Hervs and Colon Cancermentioning

confidence: 99%

Do the Human Endogenous Retroviruses Play a Role in Colon Cancer?

2016

Advances in Tumor Virology

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Long terminal repeat retroelements comprise about 8% of the human genome and include the human endogenous retroviruses (HERVs). Earllier it was suspected that HERVs can become active and be involved in the process of transformation of cells, through several oncogenic mechanisms. Abnormal expression of HERVs proteins has been reported for various types of cancer, such as melanoma, breast, prostate, and germ cell cancer, in which encoded transcripts or proteins are overexpressed in the tumor tissues. However, less is known about the association between the HERVs and the colon cancer development. We review the state of the art for colon cancer with respect to the HERVs that can be considered as an open area of investigation, potentially leading to future innovative diagnostic and therapeutic approaches.

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Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers

Cited by 77 publications

References 49 publications

Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency

Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency

Molecular functions of human endogenous retroviruses in health and disease

Do the Human Endogenous Retroviruses Play a Role in Colon Cancer?

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