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

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.

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

“…Additionally, HIF1A-AS1 recruits pYB-1 to the mRNA of HIF1α , promoting its translation, facilitating glycolysis and enhancing the resistance of pancreatic cancer cells to gemcitabine (a nucleoside antimetabolite) [ 128 ]. Likewise, lncRNAs that interact with YB-1 have been successively identified in liver cancer [ 129 ], gastric cancer [ 130 ], lymphoma [ 131 ], nasopharyngeal cancer [ 132 ], esophageal squamous cell carcinoma [ 133 ], melanoma [ 134 ], and clear cell renal cell carcinoma [ 135 ]. In addition, lncRNA PVT1 indirectly promotes YB-1 expression by sponging miR-216a-5p in colorectal cancer [ 136 ].…”

Overexpression of lncRNA TCLlnc1 in gastric cancer predicts postoperative distant recurrence and poor survival

“…We showed that the increased TCLlnc1 in plasma is correlated with distant metastasis of gastric cancer and may serve as a potential biomarker to diagnose gastric cancer and predict the survival of gastric cancer patients. In a recent study, Zhao et al [17] functionally characterized a novel lncRNA named TCLlnc1 in T cell lymphoma. In T cell lymphoma, TCLlnc1 is significantly overexpressed and it plays a role as the modular scaffold of YBX1 and HNRNPD complexes to promote cancer progression [17].…”

“…In a recent study, Zhao et al [17] functionally characterized a novel lncRNA named TCLlnc1 in T cell lymphoma. In T cell lymphoma, TCLlnc1 is significantly overexpressed and it plays a role as the modular scaffold of YBX1 and HNRNPD complexes to promote cancer progression [17]. However, the expression pattern of TCLlnc1 in other cancers is unknown.…”

“…TCLlnc1 was characterized as a lncRNA with oncogenic roles in T cell lymphoma, whereas its role in other diseases is unknown. We then explored the involvement of TCLlnc1 in gastric cancer [ 17 ].…”

Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma

“…Of tens of thousands of metazoan lncRNAs discovered from cDNA libraries and RNAseq data by high throughput transcriptome projects, only a handful of lncRNAs have been functionally characterized. The investigations on this small cohort of lncRNAs have demonstrated that these noncoding transcripts can serve as scaffolds or guides to regulate protein-protein or protein-DNA interactions [28][29][30][31] or can modulate post-translational modification of nonhistone proteins [32]. Moreover, lncRNAs are capable of controlling microRNAs (miRNAs) [33][34][35], and function as enhancers to influence gene transcription, when transcribed from the enhancer regions (enhancer RNA) [36][37][38] or their neighboring loci (noncoding RNA activator) [39,40].…”