Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells

Abstract

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT–qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

Transcriptome Analysis of Human Endogenous Retroviruses at Locus-Specific Resolution in Non-Small Cell Lung Cancer

“…Families with a higher percentage of differentially expressed HERVs included HERV-H, HERV-K, and MER4. Interestingly, up-regulation of the HERV-H and HERV-K families has been proposed as novel diagnostic biomarkers [ 47 , 48 , 49 ], while the up-regulation of the MER4 family has been linked to progression-free survival (PFS) and overall survival (OS) [ 11 ]. MER4 HERVs have also been proposed as novel biomarkers for the response to immune checkpoint inhibitors (ICI), which, currently, are becoming the standard first-line treatment of advanced NSCLC for patients with high PD-L1 expression [ 11 ].…”

“…However, the most frequently dysregulated HERV families, such as HERV-H, HERV-K, and MER4, were the same in both TCGA-LUAD and TCGA-LUSC ( Table S2 ). Notably, the upregulation of the HERV-H and HERV-K families in lung cancer has been observed by others, and it has been suggested as a potential diagnostic biomarker [ 47 , 48 , 49 ]. The expression of members of the MER4 family has been associated with differences in progression-free and overall survival.…”

Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer

“…Detecting HERV-K in blood as a non-invasive molecular marker could provide a rapid and effective method for tumor screening and assessment ( Dervan et al, 2021 ). Upregulation of HERV-K mRNA and encoded protein expression has been frequently reported in various cancers recently ( Shah et al, 2022 ; Wei et al, 2022 ; Yang et al, 2022 ). Although its role in oncogenic mechanisms is still unidentified, it is clear that abnormal HERV-K expression can be used as a diagnostic and therapeutic target for cancer ( Zhang et al, 2019 ).…”

“…The primer sequences used to amplify HERV-K(HML-2) gag , pol , env , and β-actin were obtained from a previous study ( Li et al, 2021 ). These primers have been identified to amplify the various loci of HERV-K ( Yang et al, 2022 ). Primer information is shown in Table 2 .…”

Reviewing the Potential Links between Viral Infections and TDP-43 Proteinopathies

“…These viral elements are derived from an ancestral infection of germ-line cells by exogenous retrovirus and conserve structural similarities with exogenous retroviruses, such as HIV [ 51 ]. HERV re-activation has been progressively associated with neurological disfunction, e.g., schizophrenia [ 53 ], multiple sclerosis [ 54 , 55 ] and motor neuron disease [ 56 ], as well as cancer [ 55 , 57 ]. Notably, a novel link between TDP-43 and HERV-K has been provided by two articles published few years ago.…”