HERV-R (ERV3-1) Env gene knockout reduces invasion, migration, and tumor growth in DLD1 colon cancer cells

Sep 22, 2026

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HERV-R (ERV3-1) env gene function in colon cancer was tested by knocking out the gene in the DLD1 colon cancer cell line. A 208-bp deletion was confirmed by genomic PCR and DNA sequencing, leading to markedly decreased HERV-R env expression at both RNA and protein levels. HERV-R KO cells showed significantly reduced invasion and migration abilities. In vivo, mice injected with HERV-R KO cells developed smaller tumors than controls, and mRNA-seq plus STRING analysis connected HERV-R to pathways supporting proliferation, migration, and invasion, indicating relevance for colon cancer treatment studies.

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CategoryResearch & Report

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Results

HERV-R env KO in DLD1 cells

BMB Reports BMB Rep. 2026; 59(3): 201-207 [www.bmbreports.org](www.bmbreports.org) HERV-R (ERV3-1) Env gene knockout reduces invasion, migration, and tumor growth in DLD1 colon cancer cells Min-Hye Kim1,2, Eun-Ji Ko1, HyojinAn1, Seongsoo Choi1, Heui-Soo Kim3, Sun-Hee Leem2 & Hee-Jae Cha1, * 1Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, 2Department of Biomedical, Dong-A University, Busan 49315, 3Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea The human genome contains sequences derived from endogenous retroviruses (HERVs), which constitute approximately 8% of chromosomal DNA. Most HERVs are currently inactive and noninfectious due to recombination, deletion, and mutation after integration into the host genome. However, recent studies have implicated HERVs as mutagens of intracellular genes, contributing to autoimmune diseases and tumors. Several studies have shown a significant association between HERVs and certain cancers. We focused on knocking out the HERV-R (ERV3-1) env gene in the DLD1 colon cancer cell line. A 208-bp deletion was confirmed by genomic PCR and DNA sequencing. As a result, HERV-R env gene expression was significantly lower in DLD1 HERV-R knockout (HERV-R KO) cells compared to control cells at both RNA and protein levels. Additionally, the invasion and migration abilities of HERV-R KO cells were significantly reduced. In vivo experiments on mice injected with HERV-R KO cells showed smaller tumor sizes compared to mice injected with control cells, suggesting that HERV-R env plays an important role in tumor growth. Further mRNA-seq analysis identified genes associated with cell invasion and migration. The STRING tool, which analyzes gene correlations, confirmed that HERV-R is linked to genes involved in cancer proliferation, migration, and invasion in colon cancer. This study suggests that the expression ofthe HERV-R env gene influences the tumorigenic properties of colon cancer, providing valuable evidence for potential clinical studies in colon cancer patients.[BMB Reports 2026; 59(3): 201-207] INTRODUCTION Colorectal cancer (CRC) is a malignant tumor that occurs in the mucosa of the colon and rectum and is one of the most *Corresponding author. Tel: +82-51-990-6428; Fax: +82-51-990- 3081; [E-mail: hcha@kosin.ac.kr](E-mail: hcha@kosin.ac.kr) [https://doi.org/10.5483/BMBRep.2024-0189](https://doi.org/10.5483/BMBRep.2024-0189) Received 5 December 2024, Revised 2 January 2025, Accepted 5 March 2025, Published online 31 March 2026 Keywords: Colorectal cancer, HERV-R, Knockout, mRNA-seq, Tumorigenic characteristics commonly diagnosed cancers worldwide (1, 2) . CRC detected early can be cured with surgery and follow-up medication. However, it has a high recurrence rate and can develop resistance to anticancer drugs, which increases the risk of treatment failure. Therefore, it is important to detect CRC early, as well as to conduct regular checkups and remove any detected polyps. Despite this, current diagnostic methods are limited, with only 40% of CRC cases being detected early (3). Hence, there is a need for the development of new diagnostic techniques. Retroviruses have the ability to insert their genes into the DNA of the host during replication. Over millions of years, some viruses have become part of the human genome and exist as inactivated endogenous retroviruses that can no longer replicate due to mutations, deletions, and other factors (4, 5). Endogenous retroviruses constitute approximately 8% of human chromosomal DNA and can form viral particles that have lost their ability to replicate and infect (6). However, recent studies have shown that human endogenous retroviruses (HERVs) can be expressed in certain diseases. There is a growing body of evidence suggesting a correlation between HERV expression and cancer. Cancers linked to HERV expression include lymphoma (7), br

FAQs

What approach was used to study HERV-R in DLD1 colon cancer cells?

HERV-R (ERV3-1) env gene was knocked out in DLD1 cells, and proliferation, mobility, invasiveness, and gene-expression changes were assessed.

How was the HERV-R env gene deletion verified?

A 208-bp deletion was confirmed using genomic PCR and DNA sequencing.

What were the main biological effects of HERV-R env knockout?

HERV-R env expression decreased substantially, and HERV-R KO cells exhibited significantly reduced invasion and migration, with smaller tumor sizes observed in mouse xenograft experiments.

Sep 22, 2026

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