Human endogenous retrovirus env genes: Potential blood biomarkers in lung cancer

Zare, Mokhtar; Mostafaei, Shayan; Ahmadi, Ali; Jamalkandi, Sadegh Azimzadeh; Abedini, Atefeh; Esfahani-Monfared, Zahra; Dorostkar, Ruhollah; Saadati, Mojtaba

doi:10.1016/j.micpath.2017.12.040

Cited by 35 publications

(38 citation statements)

References 26 publications

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“…HERVs are ubiquitous retroviral elements constituting up to 10% of the human genome (27), and these elements have recently been recognized as a potential biomarker in cancer (5,23,28,29). elements and malignancy has also been postulated but not yet confirmed (5).…”

Section: Discussionmentioning

confidence: 99%

“…Methylation of LTR regulatory regions is considered one of the main mechanisms responsible for controlling HERV gene transcription in normal cells (5) Indeed, altered LTR methylation has been recently demonstrated in some cancer types, suggesting that it may represent a tumor-specific trait or perhaps a prognostic marker (23,28,29). Based on our pyrosequencing analysis, Alu, and LINE-1 methylation levels were significantly lower in tumor tissues than in controls, thus confirming global hypomethylation as a typical characteristic of colon cancer (30).…”

Section: A Possible Relationship Between Dysregulation Of Herv-relatedmentioning

confidence: 99%

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Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer

et al. 2020

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Colon cancer is the fourth most common malignancy in both incidence and mortality in developed countries. Infectious agents are among the risk factors for colon cancer. Variations in human endogenous retrovirus (HERV) transcript and protein levels are associated with several types of cancers, but few studies address HERV expression in colon cancer. Fifty-eight patients with advanced-stage colon cancer were enrolled in this study. HERV-H,-K (HML-2),-P LTRs, Alu, and LINE-1 methylation levels and transcription of HERV-H,-K (HML-2), and-P env and HERV-K pol genes in normal adjacent and tumor tissues were investigated by pyrosequencing and RT-qPCR, respectively. Expression of the HERV-K (HML-2) Pol and Env proteins in selected tissues was examined by Western blotting. Associations between HERV transcript expression and methylation levels and between clinical characteristics and HERV expression were evaluated. Compared to adjacent normal tissues, LINE-1 was hypomethylated in tumor tissues (p < 0.05), whereas Alu, HERV-K (HML-2), and-H LTRs showed a decreasing trend in tumor tissue compared to normal tissue, though without a significant difference. The transcription levels of HERV env and pol genes were similar. However, the HERV-K (HML-2) Pol protein was more highly expressed (p < 0.01) in surrounding normal tissues, but the HERV-K (HML-2) Env protein was only expressed in tumor tissues. Although HERV LTR methylation and gene expression did not show significant differences between tumor and normal tissues, HERV protein expression differed greatly. Pol protein expression in normal cells may induce reverse transcription and subsequent integration into the host genome, likely favoring cell transformation; in contrast, the Env protein in tumor tissue may contribute to cancer progression through cell-to-cell fusion.

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Section: Discussionmentioning

confidence: 99%

Section: A Possible Relationship Between Dysregulation Of Herv-relatedmentioning

confidence: 99%

Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer

et al. 2020

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“…Viral products of many HERVs, such as the K, H, R, and T families, have been detected in cells, blood and tissues of patients with lung cancer or breast cancers. Levels of HERVs transactivation have been shown to be much higher in these patients than those in healthy volunteers 25 – 27 . The positive correlation of HERVs transactivation with cancer is strongly supported by the observation that some specific antibodies or shRNAs against HERV-K possess inhibitory effect on the growth of cancer cells in vitro and in vivo 28 , 29 .…”

Section: Introductionmentioning

confidence: 87%

“…The positive correlation of HERVs transactivation with cancer is strongly supported by the observation that some specific antibodies or shRNAs against HERV-K possess inhibitory effect on the growth of cancer cells in vitro and in vivo 28 , 29 . Thus, HERVs could be considered as suitable prognostic markers for a variety of malignant diseases, such as lung cancers and HCC 17 , 25 . Additional studies have found that Np9 and Rec proteins of HERV-K physically and functionally interact with the promyelocytic leukemia zinc finger (PLZF) tumor suppressor to regulate cancer cell proliferation and survival through altering the expression of the c- Myc proto-oncogene 30 , 31 .…”

Section: Introductionmentioning

confidence: 99%

Transactivation of human endogenous retroviruses by tumor viruses and their functions in virus-associated malignancies

2019

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Human endogenous retroviruses (HERVs), viral-associated sequences, are normal components of the human genome and account for 8–9% of our genome. These original provirus sequences can be transactivated to produce functional products. Several reactivated HERVs have been implicated in cancers and autoimmune diseases. An emerging body of literature supports a potential role of reactivated HERVs in viral diseases, in particular viral-associated neoplasms. Demystifying studies on the mechanism(s) of HERV reactivation could provide a new framework for the development of treatment and prevention strategies targeting virus-associated tumors. Although available data suggest that co-infection by other viruses, such as Kaposi’s Sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), may be a crucial driving force to transactivate HERV boom, the mechanisms of action of viral infection-induced HERV transactivation and the contributions of HERVs to viral oncogenesis warrant further studies. Here, we review viral co-infection contributes to HERVs transactivation with focus on human viral infection associated oncogenesis and diseases, including the abilities of viral regulators involved in HERV reactivation, and physiological effects of viral infection response on HERV reactivation.

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“…Other cancers have also been related to HERV-K, like renal carcinoma [32,33], lymphoma [34], leukaemia [35], melanoma [36,37], sarcoma [38], endometrial [39] or lung cancer [40]. However, we chose to focus on the more extensively researched ones.…”

Section: Herv-kmentioning

confidence: 99%

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy

Bermejo

Ragonnaud

Daradoumis

et al. 2020

IJMS

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Cancer is a major challenge in our societies, according to the World Health Organization (WHO) about 1/6 deaths were cancer related in 2018 and it is considered the second leading cause of death globally. Immunotherapies have changed the paradigm of oncologic treatment for several cancers where the field had fallen short in providing competent therapies. Despite the improvement, broadly acting and highly effective therapies capable of eliminating or preventing human cancers with insufficient mutated antigens are still missing. Adenoviral vector-based vaccines are a successful tool in the treatment of various diseases including cancer; however, their success has been limited. In this review we discuss the potential of adenovirus as therapeutic tools and the current developments to use them against cancer. More specifically, we examine how to use them to target endogenous retroviruses (ERVs). ERVs, comprising 8% of the human genome, have been detected in several cancers, while they remain silent in healthy tissues. Their low immunogenicity together with their immunosuppressive capacity aid cancer to escape immunosurveillance. In that regard, virus-like-vaccine (VLV) technology, combining adenoviral vectors and virus-like-particles (VLPs), can be ideal to target ERVs and elicit B-cell responses, as well as CD8+ and CD4+ T-cells responses.

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Human endogenous retrovirus env genes: Potential blood biomarkers in lung cancer

Cited by 35 publications

References 26 publications

Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer

Human Endogenous Retroviruses Long Terminal Repeat Methylation, Transcription, and Protein Expression in Human Colon Cancer

Transactivation of human endogenous retroviruses by tumor viruses and their functions in virus-associated malignancies

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy

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