Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town 7700, South Africa.
Genes (Basel). 2021 Aug 24;12(9):1302. doi: 10.3390/genes12091302.
Viruses and viral components have been shown to manipulate the expression of host microRNAs (miRNAs) to their advantage, and in some cases to play essential roles in cancer pathogenesis. Burkitt lymphoma (BL), a highly aggressive B-cell derived cancer, is significantly over-represented among people infected with HIV. This study adds to accumulating evidence demonstrating that the virus plays a direct role in promoting oncogenesis. A custom miRNA PCR was used to identify 32 miRNAs that were differently expressed in Burkitt lymphoma cells exposed to HIV-1, with a majority of these being associated with oncogenic processes. Of those, hsa-miR-200c-3p, a miRNA that plays a crucial role in cancer cell migration, was found to be significantly downregulated in both the array and in single-tube validation assays. Using an in vitro transwell system we found that this downregulation correlated with significantly enhanced migration of BL cells exposed to HIV-1. Furthermore, the expression of the ZEB1 and ZEB2 transcription factors, which are promotors of tumour invasion and metastasis, and which are direct targets of hsa-miR-200c-3p, were found to be enhanced in these cells. This study therefore identifies novel miRNAs as role players in the development of HIV-associated BL, with one of these miRNAs, hsa-miR-200c-3p, being a candidate for further clinical studies as a potential biomarker for prognosis in patients with Burkitt lymphoma, who are HIV positive.
病毒和病毒成分已被证明可以操纵宿主 microRNA（miRNA）的表达，使其受益，在某些情况下，在癌症发病机制中发挥重要作用。伯基特淋巴瘤（BL）是一种高度侵袭性的 B 细胞来源的癌症，在感染 HIV 的人群中明显更为常见。这项研究增加了越来越多的证据，证明病毒在促进致癌作用方面发挥直接作用。使用定制的 miRNA PCR 来鉴定在暴露于 HIV-1 的 Burkitt 淋巴瘤细胞中表达不同的 32 个 miRNA，其中大多数与致癌过程有关。在这些 miRNA 中，hsa-miR-200c-3p 是一种在癌细胞迁移中起关键作用的 miRNA，在阵列和单管验证试验中均发现其显著下调。使用体外 Transwell 系统，我们发现这种下调与 BL 细胞暴露于 HIV-1 时迁移能力的显著增强相关。此外，ZEB1 和 ZEB2 转录因子的表达也增强了，这些转录因子是肿瘤侵袭和转移的促进因子，也是 hsa-miR-200c-3p 的直接靶标。因此，这项研究确定了新的 miRNA 作为 HIV 相关 BL 发展中的作用因子，其中 hsa-miR-200c-3p 是进一步临床研究的候选物，作为 HIV 阳性的 Burkitt 淋巴瘤患者预后的潜在生物标志物。
