Expressional activation and functional roles of human endogenous retroviruses in cancers

Human endogenous retroviruses (HERVs) are widely believed to be remnants of ancestral germ line infections by exogenous retroviruses. Although HERVs are deemed as "nonfunctional DNAs" due to loss of most of their viral protein coding capacity during evolution as part of the human genome, cumulative evidences are showing the expressional activation and potential roles of HERVs in diseases especially cancers. Work by other researchers and us has observed the dysregulation of HERVs in cancers, identified new HERV-related genes, and revealed their potential importance in cancer development. Here, we summarized the current knowledge on the mechanisms of the expressional activation and functional roles of HERVs, with a focus on the H family HERV (HERV-H), in carcinogenesis. HERV expression is regulated by external chemical or physical substances and exogenous virus infection, as well as host factors such as epigenetic DNA methylation, transcription factors, cytokines, and small RNAs. Diverse roles of HERVs have been proposed by acting in the forms of noncoding RNAs, proteins, and transcriptional regulators during carcinogenesis. However, much remains to be learnt about the contributions of HERVs to human cancers. More investigation is warranted to elucidate the functions of these "fossil remnants" yet important viral DNAs in the human genome.