Engel Kristina, Wieland Lisa, Krüger Anna, Volkmer Ines, Cynis Holger, Emmer Alexander, Staege Martin S
Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
Department of Neurology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Front Oncol. 2021 Apr 29;11:637981. doi: 10.3389/fonc.2021.637981. eCollection 2021.
Endogenous retroviruses (ERVs) are becoming more and more relevant in cancer research and might be potential targets. The oncogenic potential of human ERVs (HERVs) has been recognized and includes immunosuppression, cell fusion, antigenicity of viral proteins, and regulation of neighboring genes. To decipher the role of HERVs in human cancers, we used a bioinformatics approach and analyzed RNA sequencing data from the LL-100 panel, covering 22 entities of hematopoietic neoplasias including T cell, B cell and myeloid malignancies. We compared HERV expression in this panel with hematopoietic stem cells (HSCs), embryonic stem cells (ESCs) and normal blood cells. RNA sequencing data were mapped against a comprehensive synthetic viral metagenome with 116 HERV sequences from 14 different HERV families. Of these, 13 HERV families and elements were differently expressed in malignant hematopoietic cells and stem cells. We found transcriptional upregulation of HERVE family in acute megakaryocytic and erythroid leukemia and of HERVFc family in multiple myeloma/plasma cell leukemia (PCL). The HERVFc member HERVFc-1 was found transcriptionally active in the multiple myeloma cell line OPM-2 and also in the Hodgkin lymphoma cell line L-428. The expression of HERVFc-1 in L-428 cells was validated by qRT-PCR. We also confirm transcriptional downregulation of ERV3 in acute megakaryocytic and erythroid leukemia, and HERVK in acute monocytic and myelocytic leukemia and a depression of HERVF in all malignant entities. Most of the higher expressed HERV families could be detected in stem cells including HERVK (HML-2), HERV-like, HERVV, HERVT, ERV9, HERVW, HERVF, HERVMER, ERV3, HERVH and HERVPABLB.
内源性逆转录病毒（ERVs）在癌症研究中变得越来越重要，可能是潜在的靶点。人类内源性逆转录病毒（HERVs）的致癌潜力已得到认可，包括免疫抑制、细胞融合、病毒蛋白的抗原性以及对邻近基因的调控。为了解HERVs在人类癌症中的作用，我们采用生物信息学方法，分析了LL-100样本组的RNA测序数据，该样本组涵盖了22种造血系统肿瘤实体，包括T细胞、B细胞和髓系恶性肿瘤。我们将该样本组中的HERV表达与造血干细胞（HSCs）、胚胎干细胞（ESCs）和正常血细胞进行了比较。RNA测序数据与一个包含来自14个不同HERV家族的116个HERV序列的综合合成病毒宏基因组进行比对。其中，13个HERV家族和元件在恶性造血细胞和干细胞中表达不同。我们发现HERVE家族在急性巨核细胞和红白血病中表达上调，HERVFc家族在多发性骨髓瘤/浆细胞白血病（PCL）中表达上调。发现HERVFc成员HERVFc-1在多发性骨髓瘤细胞系OPM-2以及霍奇金淋巴瘤细胞系L-428中具有转录活性。通过qRT-PCR验证了HERVFc-1在L-428细胞中的表达。我们还证实了ERV3在急性巨核细胞和红白血病中表达下调，HERVK在急性单核细胞和髓细胞白血病中表达下调，以及HERVF在所有恶性实体中表达降低。大多数高表达的HERV家族可以在干细胞中检测到，包括HERVK（HML-2）、HERV样、HERVV、HERVT、ERV9、HERVW、HERVF、HERVMER、ERV3、HERVH和HERVPABLB。
