Human endogenous retroviruses env gene expression and long terminal repeat methylation in colorectal cancer patients

Dolci, Maria; Favero, Chiara; Tarantini, Letizia; Villani, Sonia; Bregni, Marco; Signorini, Lucia; Valle, A Della; Crivelli, Filippo; D’Alessandro, Sarah; Ferrante, Pasquale; Bollati, Valentina; Delbue, Serena

doi:10.1007/s00430-020-00662-6

Cited by 9 publications

(22 citation statements)

References 42 publications

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“…Baseline characteristics of the cohort are presented by absolute numbers and frequencies and medians [1st−3rd quartile] for categorical and continuous variables, respectively. The statistical methods used to analyze and compare HERV LTR, Alu, and LINE-1 methylation levels as well as HERV env and pol gene expression in cancer and normal tissues have been previously reported (19). Possible associations between HERV LTR methylation levels or HERV gene expression in tumor tissues and the baseline characteristics of the patients were also investigated as previously reported (19).…”

Section: Discussionmentioning

confidence: 99%

“…The statistical methods used to analyze and compare HERV LTR, Alu, and LINE-1 methylation levels as well as HERV env and pol gene expression in cancer and normal tissues have been previously reported (19). Possible associations between HERV LTR methylation levels or HERV gene expression in tumor tissues and the baseline characteristics of the patients were also investigated as previously reported (19). HERV-K Pol and HERV-K Env protein expression in cancer and normal tissues was assessed and compared using ImageJ, GraphPad Prism, and paired Student's t-tests, as appropriate.…”

Section: Discussionmentioning

confidence: 99%

“…Methylation levels of HERV-H, HERV-K (HML-2), HERV-P, and HERV-W LTRs as well as methylation levels of Alu and LINE-1 sequences were evaluated by pyrosequencing using DNA isolated from the surgical specimens (cancer tissues and normal tissues), as previously described (19,21,22).…”

Section: Herv-h -K (Hml-2) -P and -W Ltr Alu And Line-1 Methylatmentioning

confidence: 99%

“…The sequences of the PCR primers are summarized in Table 1, which also indicates their location and similarity on the human chromosomes (19,23,24). The primers were subjected to validation, following the manuscript by Perot and colleagues (25).…”

Section: Herv-h -K (Hml-2) -P Env and Herv-k (Hml-2) Pol Gene Exprmentioning

confidence: 99%

“…Nonetheless, data with regard to colon cancer are scarce and currently limited to a few reports showing overexpression of HERV-H genes in tumor tissues compared to normal tissues retrieved from negative surgical margins (17). The association between HERV-P and colon cancer was also investigated previously, with opposite findings (18,19).…”

Section: Introductionmentioning

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: Discussionmentioning

confidence: 99%

Section: Herv-h -K (Hml-2) -P and -W Ltr Alu And Line-1 Methylatmentioning

confidence: 99%

Section: Herv-h -K (Hml-2) -P Env and Herv-k (Hml-2) Pol Gene Exprmentioning

confidence: 99%

Section: Introductionmentioning

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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Human polyomaviruses genomes in clinical specimens of colon cancer patients

Dolci

Signorini

Toumi

et al. 2021

Journal of Medical Virology

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Colon cancer is the third cause of cancer death in the developed countries. Some environmental factors are involved in its pathogenesis, including viral infections. The possible involvement of human polyomaviruses (HPyVs) in colon cancer pathogenesis has been previously reported, leading to inconsistent conclusions. Clinical specimens were collected from 125 colon cancer patients. Specifically, 110 tumor tissues, 55 negative surgical margins, and 39 peripheral blood samples were analyzed for the presence of six HPyVs: JC polyomavirus (JCPyV), BK polyomavirus (BKPyV), Merkel cell PyV (MCPyV), HPyV −6, −7, and −9 by means of DNA isolation and subsequent duplex Real Time quantitative polymerase chain reaction. HPyVs genome was detected in 33/204 samples (16.2%): the significant higher positivity was found in tumor tissues (26/110, 23.6%), followed by negative surgical margins (3/55, 5.5%, p < .05), and peripheral blood mononuclear cells (PBMCs) (4/39; 10.3%).HPyVs load was statistically higher only in the tumor tissues compared to negative surgical margins (p < .05). Specifically, MCPyV was detected in 19.1% (21/110) of tumor tissues, 3.6% (2/55) of negative surgical margins (p < .05), and 7.7% (3/39) of PBMCs; HPyV-6 in 2.7% (3/110) of tumor tissues, and 1.8% (1/55) of negative surgical margins; one tumor tissue (1/110, 0.9%) and one PBMCs sample (1/39, 2.6%) were positive for BKPyV; JCPyV was present in 0.9% (1/110) of tumor tissues.HPyV-7 and 9 were not detected in any sample. High prevalence and load of MCPyV genome in the tumor tissues might be indicative of a relevant rather than bystander role of the virus in the colon tumorigenesis.

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Human endogenous retroviruses in cancer: Oncogenesis mechanisms and clinical implications

Kitsou

Λάγιου

Magiorkinis

2022

Journal of Medical Virology

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Human Endogenous Retroviruses (HERVs) are viral sequences integrated into the human genome, resulting from the infection of human germ‐line cells by ancient exogenous retroviruses. Despite losing their replication and retrotransposition abilities, HERVs appear to have been co‐opted in human physiological functions while their aberrant expression is linked to human disease. The role of HERVs in multiple malignancies has been demonstrated, however, the extent to which HERV activation and expression participate in the development of cancer is not yet fully comprehended. In this review article, we discuss the presumed role of HERVs in carcinogenesis and their promising diagnostic and prognostic implications. Additionally, we explore recent data on the HERVs in cancer therapeutics, either through the manipulation of their expression, to induce antitumor innate immunity responses or as cancer immunotherapy targets. Finally, more precise and higher resolution high‐throughput sequencing approaches will further elucidate HERV participation in human physiological and pathological processes.

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Human endogenous retroviruses env gene expression and long terminal repeat methylation in colorectal cancer patients

Cited by 9 publications

References 42 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

Human polyomaviruses genomes in clinical specimens of colon cancer patients

Human endogenous retroviruses in cancer: Oncogenesis mechanisms and clinical implications

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