Long Non-Coding RNAs and Circular RNAs in the Pathobiology of T-Cell Lymphoma

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10-15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor-β (TGF-β) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma.