MicroRNA 21 Expression Levels in HIV Negative and HIV Positive Diffuse Large B Cell Lymphoma Phillips P 1 , Mcgrath E 1 , Sekar D 2 , Sookhayi R 1 , Govender D 1 , Mohamed Z 3 , Zerbini LF 2 and Naidoo R 1 1 Division of Anatomical Pathology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town/National Health Laboratory Service, Groote Schuur Hospital, South Africa 2 Cancer Genomics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), South Africa 3 Department of Radiation Oncology, University of Cape Town, Groote Schuur Hospital, South Africa * Corresponding author: Richard Naidoo, Division of Anatomical Pathology, Department of Clinical Laboratory Sciences Faculty of Health Sciences University of Cape Town Anzio Road, Observatory7925, Cape Town, Western Cape, South Africa, Tel: 27214047615, Fax: 27214047611, E-mail: Richard.Naidoo@uct.ac.za Rec Date: February 23, 2015, Acc Date: March 11, 2015, Pub Date: March 14, 2015 Copyright: © 2015 Phillips P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease with various morphological and molecular subtypes. It commonly occurs in the elderly as well as in people infected with HIV. According to the Hans' algorithm DLBCL can be classified prognostically into the favourable germinal centre (GC) subtype and the unfavourable non- GC subtype. The disease tends to be more aggressive in HIV infected individuals. Research on DLBCL has been largely conducted on HIV negative samples and it is still unclear how HIV affects the molecular mechanisms of the disease. We conducted a study to compare the expression levels of miR-21 in HIV negative and HIV positive DLBCL patients. Our results suggest that miR-21 expression levels are higher in HIV positive cases of DLBCL. We did not observe any statistically significant difference in miR-21 levels between DLBCL subtypes in both HIV negative and positive cases. Favourable prognosis in HIV negative patients was associated with high miR-21 expression and the reverse was true in HIV positive patients. In conclusion, our results indicate that HIV infection may affect the expression of miR-21 in DLBCL. This highlights the need for further studies on HIV positive DLBCL as the prognostic significance of miR-21 expression level may differ depending on the HIV status. Keywords: B-cell lymphoma; Micro RNA; Prognosis; HIV; miR-21; DLBCL Introduction Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) comprising of 30% of all NHL [1]. The disease shows marked heterogeneity, with morphological and molecular variants [2,3], making it difficult to treat. DLBCL is divided into two histological subtypes with prognostic significance according to the Hans' algorithm. The non-germinal centre (non-GC) subtype has a worse prognosis than the germinal centre B cell like (GC) subtype [4]. Recent data suggests that HIV gp120 induces B cells expressing mannose C type lectin receptors (MCLRs) to undergo immunoglobulin class switching by increasing the expression of activation-induced cytidine deaminase [5]. Chronic B-cell activation in HIV infection is driven by the production of B-cell stimulating cytokines which are secreted by gp120 bound monocytes [6]. These cytokines act by upregulating MCLRs on the surface of B cells, thus creating chronic B cell activation [5]. Therefore, people infected with HIV are at an increased risk of developing B cell NHL [7]. DLBCL is the most common NHL diagnosed in HIV infected individuals [8,9]. MicroRNAs are non-coding RNA molecules that silence the expression of target genes [10]. Gene silencing is achieved by imperfect or perfect pairing of microRNA with3UTR of target mRNA thereby resulting in inhibition of translation or degradation, respectively [11,12]. They are transcribed as long transcripts and processed by the enzymes Drosha and Dicer into microRNA duplexes. The functional strand of the duplex is loaded into the RNA- induced silencing complex enzyme (RISC) for gene silencing [10]. MicroRNAs play a role in diverse biological processes including development, cell growth and apoptosis [11,13,14]. Their expression levels are usually disrupted during malignancy [12], making them crucial regulators of the cell cycle and potential biomarkers for cancer [15]. MicroRNA 21 (miR-21) is overexpressed in most solid malignant neoplasms such as carcinomas of the breast, pancreas, lung, stomach and prostate, and glioblastomas [11,16-18]. miR-21 is involved in tumourigenesis [17], tumour progression [19], and metastasis [20]. Data generated by Thapa and colleagues reveal that the levels of miR-21 are elevated in circulating B cells of HIV positive individuals who eventually develop NHL in less than three years [15]. An above normal increase in the expression of miR-21 has been observed in cell lines, tissue [21] and serum [22,23] of DLBCL patients. Given the high rate of HIV infection in Southern Africa and the increased risk of acquiring DLBCL in HIV positive individuals; there is little research on miR-21 expression in DLBCL of HIV positive individuals. Therefore, we conducted a study to compare the expression levels of miR-21 in DLBCL in HIV positive and HIV negative individuals, and also to determine its prognostic potential in HIV positive DLBCL since no data is currently available in this particular cohort. Hereditary Genetics: Current Research Phillips, et al., Hereditary Genet 2015, 4:2 http://dx.doi.org/10.4172/2161-1041.1000143 Research Article Open Access Hereditary Genet ISSN:2161-1041 HGCR, an open access journal Volume 4 • Issue 2 • 1000143