MicroRNAs and long non-coding RNAs In T-cell lymphoma: Mechanisms, pathway, therapeutic opportunities

Abstract

T-cell lymphomas represent non-Hodgkin lymphomas distinguished by the uncontrolled proliferation of malignant T lymphocytes. Classifying these neoplasms and the ongoing investigation of their underlying biological mechanisms remains challenging. Significant subtypes encompass peripheral T-cell lymphomas, anaplastic large-cell lymphomas, cutaneous T-cell lymphomas, and adult T-cell leukemia/lymphoma. A systematic literature survey used electronic databases, including PubMed, Springer Link, Google Scholar, and Web of Science. Search keywords included "T-cell lymphoma," "therapeutic approaches," "RNA therapeutics," "microRNA," and "signaling pathways". T-cell lymphomas are believed to arise from a complex interplay of genetic predispositions and environmental factors. Epstein-Barr virus (EBV) and Human T-cell leukemia virus-1 (HTLV-1), have been implicated as potential etiologic agents. While the exact molecular mechanisms are under investigation, T-cell lymphomas are distinguished by aberrant proliferation of T-cells resulting from dysregulated gene expression. Contemporary research has emphasized the significance of non-coding RNAs, including microRNAs and long non-coding RNAs, in the etiology and advancement of T-cell lymphomas. Certain miRNAs function as tumor suppressors (e.g., miR-451, miR-31, miR-150, miR-29a), while others can act as oncogenes (e.g., miR-223, miR-17–92, miR-155). Additionally, lcRNAs are responsible for modulating gene expression, and their influence on T-cell function suggests their potential outcome as therapeutic targets.

Current therapeutic strategies for T-cell lymphomas predominantly rely on chemotherapy, with emerging modalities encompassing immunotherapy and targeted therapies. Despite these advancements, a substantial subset of T-cell lymphomas remains challenging to manage, especially those in advanced stages or refractory to conventional treatments. RNA-based therapeutics represent a promising strategy, offering many advantages such as targeted therapy, potential for personalized medicine, reduced side effects, rapid development, and synergy with other therapies while facing challenges in delivery, immune response, and specificity. Future research should focus on improving delivery systems, modulating immune responses, and optimizing production to unlock its full potential. This review comprehensively explored T-cell lymphomas, delving into their classification, pathogenesis, and existing therapeutic options. Additionally, we explore the evolving function of non-coding RNAs in the pathogenesis of T-cell lymphoma. Furthermore, we discuss the potential of RNA-based therapeutics as a promising treatment strategy.