Zhang Lin, Xu Hong-Gui, Lu Chao
Department of Pediatrics, the First Affiliated Hospital of Nanjing Medical University , Nanjing , China.
Leuk Lymphoma. 2014 Jun;55(6):1373-82. doi: 10.3109/10428194.2013.829574. Epub 2013 Aug 28.
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy with a poor prognosis. It has been shown that long non-coding RNA (lncRNA) plays an important role in tumorigenesis. Here, we characterized a novel lncRNA, T-ALL-R-LncR1, with whole-transcriptome deep sequencing from the Jurkat leukemic T-cell line. T-ALL-R-LncR1 was not observed in human normal tissues. However, an obvious expression was observed in some tumor tissues. T-ALL-R-LncR1 was markedly expressed in neoplastic T lymphocytes of 11 cases out of 21 children with T-ALL, indicating that T-ALL-R-LncR1 might be associated with T-ALL. T-ALL-R-LncR1 knockdown predisposed Jurkat cells to undergo pro-apoptotic factor Par-4-induced apoptosis. Further studies revealed that T-ALL-R-LncR1 knockdown facilitated the formation of a Par-4/THAP1 protein complex, resulting in the activation of caspase-3 and an increase of pro-apoptotic Smac protein in T-ALL cells. Our studies indicate a potential role of suppressing the novel long non-coding RNA T-ALL-R-LncR1 in the therapy of human T-ALL.
T细胞急性淋巴细胞白血病（T-ALL）是一种预后较差的血液系统恶性肿瘤。研究表明，长链非编码RNA（lncRNA）在肿瘤发生过程中发挥着重要作用。在此，我们通过对Jurkat白血病T细胞系进行全转录组深度测序，鉴定了一种新型lncRNA，即T-ALL-R-LncR1。在人类正常组织中未观察到T-ALL-R-LncR1。然而，在一些肿瘤组织中观察到其明显表达。在21例儿童T-ALL患者中，有11例患者的肿瘤性T淋巴细胞中T-ALL-R-LncR1显著表达，这表明T-ALL-R-LncR1可能与T-ALL相关。敲低T-ALL-R-LncR1使Jurkat细胞易于发生促凋亡因子Par-4诱导的凋亡。进一步研究表明，敲低T-ALL-R-LncR1促进了Par-4/THAP1蛋白复合物的形成，导致T-ALL细胞中caspase-3激活以及促凋亡Smac蛋白增加。我们的研究表明，抑制新型长链非编码RNA T-ALL-R-LncR1在人类T-ALL治疗中具有潜在作用。
