Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression

SIMPLE SUMMARY: Retroelements are endogenous DNA elements present in the human genome. They have a key role in tumorigenesis and cancer progression. Several studies have reported their expression as biomarkers and immunotherapeutic targets to cancer. Their expression can be induced by epigenetic alteration and virus infections. Retroelement overexpression has been shown in distinct types of cancer, such as breast cancer, melanoma, renal cell carcinoma and prostate cancer. However, studies on other specific types of cancer, such as in cervical cancer, are scarce. Here we explored the expression of retroelements in cervical cancer as well as their interplay with HPV infection and their association with expression of neighboring genes. We find expression of retroelements specific to cervical cancer, associated with tumor histological type and HPV infection, as a new target as biomarkers and for immune therapy approaches. ABSTRACT: Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.