Human Endogenous Retrovirus Expression Is Upregulated in the Breast Cancer Microenvironment of HIV Infected Women: A Pilot Study.
Human Endogenous Retrovirus Expression Is Upregulated in the Breast Cancer Microenvironment of HIV Infected Women: A Pilot Study.
复制标题
DOI：
10.3389/fonc.2020.553983
复制
发表时间：
2020
影响因子：
4.7
通讯作者：
de Mulder Rougvie M
中科院分区：
文献类型：
--
作者：
Curty G;Beckerle GA;Iñiguez LP;Furler RL;de Carvalho PS;Marston JL;Champiat S;Heymann JJ;Ormsby CE;Reyes-Terán G;Soares MA;Nixon DF;Bendall ML;Leal FE;de Mulder Rougvie M
在艾滋病毒感染者（PLWH）中，慢性炎症除了导致免疫反应失调和减弱外，还可能导致癌症的发生和进展。HIV感染还导致人内源性逆转录病毒（HERV）的转录增加，这可能增加炎症环境并产生具有促炎细胞因子高表达的肿瘤生长抑制环境。为了确定HIV感染对乳腺癌微环境中HERV表达的影响，我们对来自HIV阴性和HIV阳性女性的福尔马林固定石蜡包埋（FFPE）乳腺癌样本的总RNA进行测序，以进行转录组和逆转录组分析。我们从FFPE样品中进行RNA提取、文库制备和总RNA测序（RNA-seq）。RNA-seq分析显示了185个差异表达的基因：181个宿主基因（178个上调和3个下调）和HIV阳性样本中4个上调的HERV转录本。我们还探索了HERV表达对其邻近乳腺癌发展基因（BRCA 1，CCND 1，NBS 1/NBN，RAD 50，KRAS，PI 3 K/PIK 3CA）和长链非编码RNA表达（AC060780.1，也称为RP 11 -242D8.1）的影响。我们发现HERV表达与RAD 50和AC060780.1显著正相关，这表明HERV在调节PLWH乳腺癌基因中可能起作用。此外，我们发现免疫系统，细胞外基质组织和代谢信号基因在HIV阳性乳腺癌中上调。总之，我们的研究结果提供了证据，转录和逆转录的变化，乳腺癌从PLWH相比，非艾滋病毒乳腺癌，包括失调的HERVs，表明乳腺癌微环境的病毒的间接影响。
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.
登录
查看更多内容
HIV精英控制器中的抗HERV-K（HML-2）衣壳抗体反应。
影响因子：
3.3
作者：
de Mulder M;SenGupta D;Deeks SG;Martin JN;Pilcher CD;Hecht FM;Sacha JB;Nixon DF;Michaud HA
通讯作者：
Michaud HA
影响因子：
11.2
作者：
Chiu WT;Lee HT;Huang FJ;Aldape KD;Yao J;Steeg PS;Chou CY;Lu Z;Xie K;Huang S
通讯作者：
Huang S
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5.2
作者：
Balestrieri E;Argaw-Denboba A;Gambacurta A;Cipriani C;Bei R;Serafino A;Sinibaldi-Vallebona P;Matteucci C
通讯作者：
Matteucci C
影响因子：
5.2
作者：
Douville RN;Nath A
通讯作者：
Nath A