Human Endogenous Retrovirus Expression Is Upregulated in the Breast Cancer Microenvironment of HIV Infected Women: A Pilot Study.
| Publication Type | Academic Article |
| Authors | Curty G, Beckerle G, Iñiguez L, Furler R, de Carvalho P, Marston J, Champiat S, Heymann J, Ormsby C, Reyes-Terán G, Soares M, Nixon D, Bendall M, Leal F, de Mulder Rougvie M |
| Journal | Front Oncol |
| Volume | 10 |
| Pagination | 553983 |
| Date Published | 10/22/2020 |
| ISSN | 2234-943X |
| Abstract | In people living with HIV (PLWH), chronic inflammation can lead to cancer initiation and progression, besides driving a dysregulated and diminished immune responsiveness. HIV infection also leads to increased transcription of Human Endogenous Retroviruses (HERVs), which could increase an inflammatory environment and create a tumor growth suppressive environment with high expression of pro-inflammatory cytokines. In order to determine the impact of HIV infection to HERV expression on the breast cancer microenvironment, we sequenced total RNA from formalin-fixed paraffin-embedded (FFPE) breast cancer samples of women HIV-negative and HIV-positive for transcriptome and retrotranscriptome analyses. We performed RNA extraction from FFPE samples, library preparation and total RNA sequencing (RNA-seq). The RNA-seq analysis shows 185 differentially expressed genes: 181 host genes (178 upregulated and three downregulated) and four upregulated HERV transcripts in HIV-positive samples. We also explored the impact of HERV expression in its neighboring breast cancer development genes (BRCA1, CCND1, NBS1/NBN, RAD50, KRAS, PI3K/PIK3CA) and in long non-coding RNA expression (AC060780.1, also known as RP11-242D8.1). We found a significant positive association of HERV expression with RAD50 and with AC060780.1, which suggest a possible role of HERV in regulating breast cancer genes from PLWH with breast cancer. In addition, we found immune system, extracellular matrix organization and metabolic signaling genes upregulated in HIV-positive breast cancer. In conclusion, our findings provide evidence of transcriptional and retrotranscriptional changes in breast cancer from PLWH compared to non-HIV breast cancer, including dysregulation of HERVs, suggesting an indirect effect of the virus on the breast cancer microenvironment. |
| DOI | 10.3389/fonc.2020.553983 |
| PubMed ID | 33194615 |
| PubMed Central ID | PMC7649802 |