Modulation of Cellular MicroRNA by HIV-1 in Burkitt Lymphoma Cells-A Pathway to Promoting Oncogenesis.

Beatrice Relebogile Ramorola,Leonardo Alves De Souza Rios,Taahira Goolam-Hoosen,Shaheen Mowla

doi:10.3390/genes12091302

Beatrice Relebogile Ramorola, Leonardo Alves De Souza Rios + Show 2 more

Open Access

https://doi.org/10.3390/genes12091302

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Journal: Genes	Publication Date: Aug 24, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: University of Cape Town

Abstract

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.

Highlights

We designed a custom microarray based on the most common miRNAs reported to be deregulated in diffuse large B-cell lymphoma and Burkitt lymphoma (Supplementary Tables S1–S3)
Among people living with HIV, these cancers represent the two most prevalent non-Hodgkin lymphomas (NHLs) within this population group
Cells derived from the Burkitt lymphoma cell line Ramos were exposed to HIV-1 AT-2, and the miR

Summary

Introduction

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play an essential role in gene regulation post-transcriptionally [1,2]. In their mature form, miRNAs are approximately 18–22 nucleotides long and are incorporated into the RNA-induced silencing complex (RISC) where they can act as guides, leading the complex to the 30 - UTR region of messenger RNA (mRNA). MiRNAs are critical for normal cellular function and what has emerged clearly in the last decade is that aberrant miRNA expression is associated with many diseases, including malignancies This is likely a result of amplification and/or deletion of specific genomic regions, with the deregulated miRNA having either an oncogenic or tumour suppressor role, affecting one or several of the cancer hallmark events [5,6]

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