Functional Bidirectionality of ERV-Derived Long Non-Coding RNAs in Humans.

Int J Mol Sci

State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100850, China.

Published: September 2024

AI Article Synopsis

  • Human endogenous retroviruses (HERVs) are remnants of ancient retrovirus infections that have been integrated into our DNA, which may have evolved to serve specific human physiological functions despite initially being considered "junk DNA."
  • Recent research highlights that the dysregulation of endogenous retrovirus elements, particularly long non-coding RNAs (lncRNAs) derived from HERVs, can play significant roles in various human diseases, especially cancer.
  • The review discusses how these lncRNAs may have both tumor-suppressive and oncogenic effects, suggesting their potential as biomarkers and therapeutic targets in cancer research, while also summarizing their roles in normal physiological processes like immune regulation and blood cell formation.

Article Abstract

Human endogenous retroviruses (HERVs) are widely recognized as the result of exogenous retroviruses infecting the ancestral germline, stabilizing integration and vertical transmission during human genetic evolution. To date, endogenous retroviruses (ERVs) appear to have been selected for human physiological functions with the loss of retrotransposable capabilities. ERV elements were previously regarded as junk DNA for a long time. Since then, the aberrant activation and expression of ERVs have been observed in the development of many kinds of human diseases, and their role has been explored in a variety of human disorders such as cancer. The results show that specific ERV elements play respective crucial roles. Among them, long non-coding RNAs (lncRNAs) transcribed from specific long-terminal repeat regions of ERVs are often key factors. lncRNAs are over 200 nucleotides in size and typically bind to DNA, RNA, and proteins to perform biological functions. Dysregulated lncRNAs have been implicated in a variety of diseases. In particular, studies have shown that the aberrant expression of some ERV-derived lncRNAs has a tumor-suppressive or oncogenic effect, displaying significant functional bidirectionality. Therefore, theses lncRNAs have a promising future as novel biomarkers and therapeutic targets to explore the concise relationship between ERVs and cancers. In this review, we first summarize the role of ERV-derived lncRNAs in physiological regulation, mainly including immunomodulation, the maintenance of pluripotency, and erythropoiesis. In addition, pathological regulation examples of their aberrant activation and expression leading to carcinogenesis are highlighted, and specific mechanisms of occurrence are discussed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476766PMC
http://dx.doi.org/10.3390/ijms251910481DOI Listing

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