HERV Modulation in Colorectal Carcinoma Patients: A Snapshot of Endogenous Retroviral Transcriptome

Grandi, Nicole

Co-prime

Writing - Original Draft Preparation

;Liu, Ching‐Hsuan

Co-prime

Writing - Review & Editing

;Chabukswar, Saili

Data Curation

;Carta, Daniele

Formal Analysis

;Yen, Yun

Supervision

;Lin, Liang‐Tzung

Penultimate

Supervision

;Tramontano, Enzo

Last

Conceptualization

2025-01-01

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Abstract

Human endogenous retroviruses (HERVs) are proviral relics of infections that affected primates' germ line. Many HERV elements retain a residual capacity to encode transcripts and proteins that have been occasionally domesticated for the host physiology. In addition, HERV transcriptional modulation is of great interest to clarify the etiology of complex disorders such as cancer, even if a few studies assessed the specific HERV loci modulated in tumor tissues. In the present work, we used a transcriptomic approach to investigate the specific expression of ~3300 HERV loci in paired tumor and normal tissues of 7 colorectal cancer (CRC) patients. A total of 102 HERVs were significantly modulated in CRC, with a general tendency towards downregulation. Of note, among the 42 upregulated HERVs 23 belonged to the HERV-H group, that is the most investigated in CRC. De novo transcriptome reconstruction and qPCR validation allowed to identify a transcript from a HERV-H locus on chromosome Xp22.3 with high specific expression in CRC samples, potentially encoding for a partial Pol protein. These results provide a detailed description of HERV transcriptional variations in CRC and its interindividual variability, identifying a HERV-H transcript that deserves further investigation for its possible impact on tumor progression.