A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes

Ping Zhao,Ying Fang,Li Wang,Anne Janin,Meng-Meng Ji,Wei-Li Zhao,Peng-Peng Xu,Chao-Fu Wang,Shu Cheng,Zi-Xun Yan,Xiao Li,Hong-Mei Yi

doi:10.1038/s41419-021-03594-y

Abstract

Long noncoding RNAs (lncRNAs) play an essential role in tumor progression. Few researches focused on the clinical and biological relevance of lncRNAs in peripheral T cell lymphoma (PTCL). In this research, a novel lncRNA (ENST00000503502) was identified overexpressed in the main subtypes of PTCL, and designated as T cell lymphoma-associated lncRNA1 (TCLlnc1). Serum TCLlnc1 was associated with extranodal involvement, high-risk International Prognostic Index, and poor prognosis of the patients. Both in vitro and in vivo, overexpression of TCLlnc1 promoted T-lymphoma cell proliferation and migration, both of which were counteracted by the knockdown of TCLlnc1 using small interfering RNAs. As the mechanism of action, TCLlnc1 directly interacted with transcription activator heterogeneous nuclear ribonucleoprotein D (HNRNPD) and Y-box binding protein-1 (YBX1) by acting as a modular scaffold. TCLlnc1/HNRNPD/YBX1 complex upregulated transcription of TGFB2 and TGFBR1 genes, activated the tumor growth factor-β signaling pathway, resulting in lymphoma progression, and might be a potential target in PTCL.

Highlights

Introduction PeripheralT cell lymphomas (PTCL) encompass a heterogeneous group of neoplasm derived from T cell lineages and represent ~10–15% of non-Hodgkin lymphoma[1], mainly including anaplastic large-cell lymphoma (ALCL)-anaplastic lymphoma kinase (ALK)-positive (ALK+ALCL), ALCL-ALK-negative (ALK−ALCL), angioimmunoblastic T cell lymphoma (AITL), and PRCLnot otherwise specified (PTCL-NOS)[2]
LncRNA candidate ENST00000503502 is clinically relevant in peripheral T cell lymphoma (PTCL) LncRNA expression profile was examined in tissue samples of ten PTCL and ten reactive hyperplasia (RH) using Arraystar Human LncRNA Microarray v2.0
The top five Long noncoding RNAs (lncRNAs) (ENST00000394174, ENST00000432567, ENST00000503502, ENST00000456305, and NR_033390) with more co-expressed oncogenes in PTCL than in RH were identified as candidate lncRNAs and assessed by qRTPCR (Supplementary Fig. 1A)

Summary

Introduction

Introduction PeripheralT cell lymphomas (PTCL) encompass a heterogeneous group of neoplasm derived from T cell lineages and represent ~10–15% of non-Hodgkin lymphoma[1], mainly including anaplastic large-cell lymphoma (ALCL)-anaplastic lymphoma kinase (ALK)-positive (ALK+ALCL), ALCL-ALK-negative (ALK−ALCL), angioimmunoblastic T cell lymphoma (AITL), and PRCLnot otherwise specified (PTCL-NOS)[2]. PTCLs are characterized by advanced disease stage at diagnosis[3], and. Studies have focused on the alterations in protein-coding genes that serve as diagnostic and therapeutic targets of PTCL7. Growing evidence suggests that noncoding RNAs are critically involved in tumor progression[8,9]. Long noncoding RNAs (lncRNAs) belong to a class of noncoding sequences >200 nucleotides in length[10] and are emerging as essential factors in the tumorigenesis and metastasis of various cancers, including hematological malignancies[11,12]. The expression of HOTAIR enhances B-lymphoma cell growth through mitogen-activated protein kinase (MAPK) and extracellular signal‐regulated kinase signaling pathway[13]. LncRNA metastasis-associated lung adenocarcinoma transcript 1 is overexpressed in hematological

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Conclusion