Abstract
Simple SummaryNon-Hodgkin’s lymphoma (NHL) is a very heterogenous class of hematological cancers, with variable patient outcomes. Therefore, there is an urgent need to develop new and more effective therapeutic approaches. MiRNAs and lncRNAs have emerged as the central gene expression regulators, and their deregulation has been reported to be involved in lymphomagenesis. Given their ability to simultaneously modulate multiple targets, they provide an attractive therapeutic approach to treat NHL patients. In this review, we discuss the scientific rationale behind miRNA/lncRNA-based therapies in NHL and the different targeting technologies, such as antisense oligonucleotides, CRISPR-Cas9, and nanomedicines.Increasing evidence has demonstrated the functional roles of miRNAs and lncRNAs in lymphoma onset and progression, either by acting as tumor-promoting ncRNAs or as tumor suppressors, emphasizing their appeal as lymphoma therapeutics. In fact, their intrinsic ability to modulate multiple dysregulated genes and/or signaling pathways makes them an attractive therapeutic approach for a multifactorial pathology like lymphoma. Currently, the clinical application of miRNA- and lncRNA-based therapies still faces obstacles regarding effective delivery systems, off-target effects, and safety, which can be minimized with the appropriate chemical modifications and the development of tumor site-specific delivery approaches. Moreover, miRNA- and lncRNA-based therapeutics are being studied not only as monotherapies but also as complements of standard treatment regimens to provide a synergic effect, improving the overall treatment efficacy and reducing the therapeutic resistance. In this review, we summarize the fundamentals of miRNA- and lncRNA-based therapeutics by discussing the different types of delivery systems, with a focus on those that have been investigated in lymphoma in vitro and in vivo. Moreover, we described the ongoing clinical trials of novel miRNA- and lncRNA-based therapeutics in lymphoma.
Highlights
Non-Hodgkin’s lymphoma (NHL) is a very heterogenous group of lymphoid malignancies originating from different stages of B-cell (~90% of the cases) and T-cell or NK-cell differentiation [1]
We provide a holistic overview of the current state of miRNA- and long noncoding RNAs (lncRNAs)-based therapeutics in lymphoma by addressing the different therapeutic strategies and delivery systems developed to boost their therapeutic efficacy and by reviewing the results of in vitro and in vivo studies of the therapeutic potential of miRNA and lncRNA
Despite the best efforts to uncover the regulatory role of miRNAs and lncRNAs in lymphoma, additional research is needed to better understand the complex functional network behind miRNAs/lncRNAs regulatory interactions during lymphomagenesis in order to translate this knowledge into clinical practice
Summary
Non-Hodgkin’s lymphoma (NHL) is a very heterogenous group of lymphoid malignancies originating from different stages of B-cell (~90% of the cases) and T-cell or NK-cell differentiation [1]. For the past few years, the unveiling of the several players and molecular mechanisms involved in lymphomagenesis has permitted the development of promising new therapeutic agents that target the agents and pathways involved in the malignant process [7,8] In this instance, noncoding RNAs (ncRNAs) have emerged as important players in lymphoma pathogenesis, with several found deregulated in lymphoma, highlighting their role as potential therapeutic strategies [9,10]. Some miRNAs have already reached clinical trials [11] Most recently, another class of ncRNAs has come into play as an important regulator of lymphoma development, demonstrating significant clinical relevance, known as long noncoding RNAs (lncRNAs) [13].
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