Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression
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Cancers
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.
Description
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.
Keywords
Retroelements, Retroelementos, Endogenous Retroviruses, Retrovirus Endógenos, HERV, Long Interspersed Nucleotide Elements, Elementos Nucleotídeos Longos e Dispersos, Elementos de Nucleótido Esparcido Largo, Uterine Cervical Neoplasms, Neoplasias do Colo do Útero, Neoplasias del Cuello Uterino, Papillomaviridae