Diagnostic significance of dysregulated miRNAs in T-cell malignancies and their metabolic roles

Abstract

T-cell malignancy is a broad term used for a diverse group of disease subtypes representing dysfunctional malignant T cells transformed at various stages of their clonal evolution. Despite having similar clinical manifestations, these disease groups have different disease progressions and diagnostic parameters. The effective diagnosis and prognosis of such a diverse disease group demands testing of molecular entities that capture footprints of the disease physiology in its entirety. MicroRNAs (miRNAs) are a group of noncoding RNA molecules that regulate the expression of genes and, while doing so, leave behind specific miRNA signatures corresponding to cellular expression status in an altered stage of a disease. Using miRNAs as a diagnostic tool is justified, as they can effectively distinguish expressional diversity between various tumors and within subtypes of T-cell malignancies. As global attention for cancer diagnosis shifts toward liquid biopsy, diagnosis using miRNAs is more relevant in blood cancers than in solid tumors. We also lay forward the diagnostic significance of miRNAs that are indicative of subtype, progression, severity, therapy response, and relapse. This review discusses the potential use and the role of miRNAs, miRNA signatures, or classifiers in the diagnosis of major groups of T-cell malignancies like T-cell acute lymphoblastic lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKTCL), and cutaneous T-cell lymphoma (CTCL). The review also briefly discusses major diagnostic miRNAs having prominent metabolic roles in these malignancies to highlight their importance among other dysregulated miRNAs.

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers

“…miRNAs play a major role in cancer progression by interacting with tumor-to-stromal interactions, immune invasion, angiogenesis, and the tumor microenvironment ( Peng and Croce, 2016 ; O’Brien et al, 2018 ). These miRNAs have multiple clinical utilities, from being used as a tool for molecular diagnosis to a method for the prognosis assessment of several cancers ( Galvão-Lima et al, 2021 ; Mondal et al, 2023 ). These miRNAs can become associated with exosomes as miRNAs shredded from tissue damage or programmed cell death can enter the bloodstream via micro-vesicles and exosomes by binding to HDL, AGO2, and LDL proteins ( Li Z. et al, 2022 ).…”

Precise diagnosis and treatment for peripheral T-cell lymphomas: From pathogenic mechanisms to innovative approaches

“…Since 2009, the Food and Drug Administration has approved several new drugs for PTCLs (e.g., pralatrexate, 17 romidepsin, 18 brentuximab vedotin, 19 and mogamulizumab 20 ). Several promising compounds have entered clinical trials (e.g., histone deacetylase inhibitor 21 , dual phosphoinositide-3-kinase (PI3K) inhibitor 22 , EZH2 inhibitor 23 , and immunomodulatory agent 24 ). However, due to limitations in our understanding of the structural biology, protein engineering, and receptor pharmacology of biomarkers, many molecules with identified pathogenic potential lack targeted agents, such as RHOA G17V mutation and TCR signaling.…”