Long Non-coding RNAs As Novel Therapeutic Agents and Biomarkers for Treating Epstein-Barr Virus Associated Diffuse Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma. It is clinically heterogeneous and highly aggressive, and may develop resistance upon relapse. Current treatments, although effective, are hampered by the robust nature of the cancer. The Epstein-Barr virus (EBV) is a ubiquitous potential oncovirus implicated in DLBCL development. Upon infecting B cells, EBV expresses oncogenic latency proteins and RNAs that have been shown to induce lymphomagenesis in vitro and in vivo. No causative link between EBV and DLBCL has been established, and more research must be conducted to clarify this issue. Interestingly, EBV-encoded RNAs and miRNAs represent a subset of latency genes that lend themselves to detailed study using transcriptomic sequencing technologies. Understanding their potential roles in B-cell transformation may elucidate cellular pathways perturbed during the progression of a DLBCL-inducing oncogenic cascade. Next, long non-coding RNAs (lncRNAs) have been identified as novel players in cancer biology. Their myriad of functions have been uncovered, and a well-studied lncRNA has been implicated in DLBCL pathology. Whole transcriptome sequencing has been suggested as a means to annotate novel lncRNAs as therapeutic targets for all primary, refractory, and EBV+ DLBCLs. Exosomal-lncRNAs may also prove useful for replacing invasive biopsy-based diagnosis of DLBCL in the clinic. Experimental designs addressing both questions were suggested, and some concerns including the inability to overexpress or efficiently deliver targeted therapies in vivo were discussed. Ultimately, it is believed that these novel transcripts may open a new frontier in personalized medicine for diseases including cancer. In vitro, in silico, and in vivo pre-clinical studies may highlight a few key lncRNAs that  can complement other therapies to treat DLBCL. Moreover, lncRNA signatures may be utilized to identify disease progression and can be combined with current markers to clarify the clinical heterogeneity of DLBCL. Thus, EBV may contribute to lymphoma onset, but lncRNAs offer a novel targetable therapeutic approach for treating DLBCL and replacing invasive diagnostic techniques.