HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia

Camargo-Forero, Nicolás; Orozco-Arias, Simón; Agudelo, Juan Manuel Pérez; Guyot, Romain

doi:10.1007/s00705-023-05747-0

Cited by 5 publications

(7 citation statements)

References 66 publications

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“…We and other researchers have shown that HERV-K envelope glycoproteins harbor immunosuppressive activity and are enriched in tumor tissues of a variety of cancers and as sociated with poor outcome [11][12][13][14][15][16]. In the present study, we, for the first time, demonstrated that subtype-specific K102-Env, but not K108-Env, is a novel serum biomarker for evaluatin g immunosuppressive status and disease stage of patients with cancer.…”

Section: Discussionsupporting

confidence: 56%

“…Previous studies have revealed that HERV-K-Env proteins are enriched in tumor tissues of a variety of cancers [11][12][13][14][15][16], and there are a number of HERV-K family members, but it is unknown whether K-Env proteins are present in circulating blood of patients with cancer. Of the HERV-K family, only HERV-K108 and HERV-K102 proviruses contain intact ORFs [10], thus, we focused on K108-Env and K102-Env in this study.…”

Section: K108-env Proteins Are Present In Serum Of Both Patients With...mentioning

confidence: 99%

“…Although high levels of HERV-K-Env in tumor tissues imply poor outcome [11][12][13][14][15][16], it is unknown whether increased circulating K102-Env in blood is associated with disease activity. We next analyzed correlation of circulating K102-Env level and cancer stage in PDAC and HCC, and we found increased circulating K102-Env proteins mainly in the sera from patients with advanced or metastatic cancer.…”

Section: Serum K102 Env Levels Are Associated With Advanced Cancersmentioning

confidence: 99%

“…Several HERV-K family members, such as HERV-K102 and HERV-K108, are unique to humans and continue to evolve [9,10]. We, and other researchers, have previously demonstrated that HERV-K envelope glycoproteins (K-Env), which consist of a surface unit (SU) and a transmembrane (TM) subunit with potential immunosuppressive activity, are enriched in tumor tissues and correlate with poor outcome in cancers that include acute myeloid leukemia (AML), pancreatic duct adenocarcinoma (PDAC), lung cancer, and glioma [11][12][13][14][15][16]. Previous studies have shown that reactivation of HERV-K is associated with immunosuppressive status in some diseases.…”

Section: Introductionmentioning

confidence: 99%

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Subtype-specific HERV-K102 envelope is a novel serum immunosuppressive biomarker and therapeutic target of cancer

Xu,

Gong,

et al. 2024

Preprint

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Background: Immune dysfunction is a hallmark of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific HERV-K102 envelope (K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. Methods: We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay for serum K102-Env. We then investigated whether K102-Env and K108-Env proteins are present in circulating blood of cancer patients. Results: We detected K108-Env in 63.33% of patients with pancreatic duct adenocarcinoma (PDAC) (n = 30) and 63% of healthy sera (n = 30). In contrast, K102-Env markedly increased in patients with PDAC, hepatocellular carcinoma (HCC), and non-small cell lung cancer (NSCLC) compared with healthy controls (p < 0.01). The positive rates of K102-Env were 34.00%, 39%, and 28.0% in PDAC, HCC, and NSCLC, respectively, whereas only 5.0% of healthy individuals had marginally increased K102-Env. In patients with PDAC, K102-Env was 36.63-fold higher than in sera of healthy controls. K102-Env significantly upregulated PD-1/PD-L1 and c-Myc expression levels of T cells. Importantly, serum K102-Env levels correlated well with advanced cancers and tumor biomarkers CA19-9 and AFP. Conclusion: These findings indicate that circulating K102-Env is a novel serum biomarker for evaluating immunosuppressive status and disease stage of patients with cancer, and it also provides a potential target for cancer immunotherapy.

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Section: Discussionsupporting

confidence: 56%

Section: K108-env Proteins Are Present In Serum Of Both Patients With...mentioning

confidence: 99%

Section: Serum K102 Env Levels Are Associated With Advanced Cancersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Subtype-specific HERV-K102 envelope is a novel serum immunosuppressive biomarker and therapeutic target of cancer

Xu,

Gong,

et al. 2024

Preprint

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“…PCAT1 is a repressor of the BRCA2 gene, which plays a pivotal role in DNA doublestrand break (DSB) repair machinery and, when silenced, allows an accumulation of PCa-related gene aberrations. 123 The retroviral history of HERVK is confirmed by their unique structures and the activation of viralinfection immune response enzymes resulting from their transposition, such as IDO1 (T-lymphocytes maturation controller), NF-κB-mediated cellular pathways, and OAS (central role in innate immune antiviral response). [124][125][126] The action of another TE, endogenous retrovirus 3 (ERV3), converges on the latter.…”

Section: Characterization Of Network Of Tes Associated With Specific ...mentioning

confidence: 99%

State‐of‐the‐art in transposable element modulation affected by drugs in malignant prostatic cancer cells

Terrazzan,

Vanini,

Ancona

et al. 2024

J of Cellular Biochemistry

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Over recent years, the investigation of transposable elements (TEs) has granted researchers a deeper comprehension of their characteristics and functions, particularly regarding their significance in the mechanisms contributing to cancer development. This manuscript focuses on prostate carcinoma cell lines and offers a comprehensive review intended to scrutinize the associations and interactions between TEs and genes, as well as their response to treatment using various chemical drugs, emphasizing their involvement in cancer progression. We assembled a compendium of articles retrieved from the PubMed database to construct networks demonstrating correlations with genes and pharmaceuticals. In doing so, we linked the transposition of certain TE types to the expression of specific transcripts directly implicated in carcinogenesis. Additionally, we underline that treatment employing different drugs revealed unique patterns of TE reactivation. Our hypothesis gathers the current understanding and guides research toward evidence‐based investigations, emphasizing the association between antiviral drugs, chemotherapy, and the reduced expression of TEs in patients affected by prostate cancer.

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Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events

Chen,

Yu,

Yang

et al. 2024

Nat Commun

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Endogenous retroviruses (ERVs) are ancient retroviral remnants integrated in host genomes, and commonly deleted through unequal homologous recombination, leaving solitary long terminal repeats (solo-LTRs). This study, analysing the genomes of 362 bird species and their reptilian and mammalian outgroups, reveals an unusually higher level of solo-LTRs formation in birds, indicating evolutionary forces might have purged ERVs during evolution. Strikingly in the order Passeriformes, and especially the parvorder Passerida, endogenous retrovirus K (ERVK) solo-LTRs showed bursts of formation and recurrent accumulations coinciding with speciation events over past 22 million years. Moreover, our results indicate that the ongoing expansion of ERVK solo-LTRs in these bird species, marked by high transcriptional activity of ERVK retroviral genes in reproductive organs, caused variation of solo-LTRs between individual zebra finches. We experimentally demonstrated that cis-regulatory activity of recently evolved ERVK solo-LTRs may significantly increase the expression level of ITGA2 in the brain of zebra finches compared to chickens. These findings suggest that ERVK solo-LTRs expansion may introduce novel genomic sequences acting as cis-regulatory elements and contribute to adaptive evolution. Overall, our results underscore that the residual sequences of ancient retroviruses could influence the adaptive diversification of species by regulating host gene expression.

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HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia

Cited by 5 publications

References 66 publications

Subtype-specific HERV-K102 envelope is a novel serum immunosuppressive biomarker and therapeutic target of cancer

Subtype-specific HERV-K102 envelope is a novel serum immunosuppressive biomarker and therapeutic target of cancer

State‐of‐the‐art in transposable element modulation affected by drugs in malignant prostatic cancer cells

Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events

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