The roles and therapeutic potential of long noncoding RNAs (lncRNAs) in acute myeloid leukemia (AML) have attracted increased attention. However, many lncRNAs have not been annotated in AML, and their predictive value for AML therapy remains unclear. In this study, we identified a novel large intergenic noncoding RNA uc002jit.1 (D43770) from a lncRNA microarray. We first proved uc002jit.1 is a target gene of nuclear factor kappa B/RELA, RELA regulated uc002jit.1 transcription by binding to its promoter. Additionally, uc002jit.1 knockdown impaired the stability of poly (ADP-ribose) polymerase 1 (PARP1) mRNA, and then reduced PARP1 protein content and PARylation level upon DNA damage, thus inhibiting DNA damage repair in AML cells. Moreover, uc002jit.1 knockdown significantly inhibited AML cells proliferation and increased the sensitivity to chemotherapeutic drugs in vitro as well as in a mouse model in vivo. Overall, our study indicated that uc002jit.1 may be associated with the occurrence and prognosis of AML and could be a new diagnostic/prognostic biomarker and therapeutic target for AML.

长非编码RNA（lncRNA）在急性髓细胞性白血病（AML）中的作用和治疗潜力已引起越来越多的关注。但是，许多lncRNA尚未在AML中进行注释，其在AML治疗中的预测价值仍不清楚。在这项研究中，我们从lncRNA微阵列中鉴定了一种新型的大型基因间非编码RNA uc002jit.1（D43770）。我们首先证明uc002jit.1是核因子κB/ RELA的靶基因，RELA通过与启动子结合来调控uc002jit.1转录。此外，uc002jit.1击倒削弱了聚（ADP-核糖）聚合酶1（PARP1）mRNA的稳定性，然后降低了DNA损伤后PARP1蛋白的含量和PARylation的水平，从而抑制了AML细胞中DNA损伤的修复。此外，uc002jit.1组合物在体外以及在体内小鼠模型中均显着抑制AML细胞增殖并增加了对化学治疗药物的敏感性。总体而言，我们的研究表明uc002jit.1可能与AML的发生和预后有关，并且可能是AML的新的诊断/预后生物标志物和治疗靶标。