Li Li, Zhao Weidong
Department of Lymphoma, Sichuan Cancer Hospital & Institute, Sichun Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No.55, Section 4, South Renmin Road, Chendu, 610041, Sichuan, China.
Food Nutrition Center, West China Hospital, Sichun University, No.37, Guoxue Xiang, Wuhou District, Chendu, 610041, Sichuan, China.
Cancer Cell Int. 2021 May 13;21(1):260. doi: 10.1186/s12935-021-01966-0.
Non-coding RNAs (ncRNAs) have been identified as key regulators during the pathogenesis and development of cancers. However, most of ncRNAs have never been explored in acute myeloid leukemia (AML).
Gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Functional assays were performed to assess the cellular processes in AML cells. The relationship between genes was verified by means of a series of mechanism assays.
Transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) was notably downregulated in AML cells, and functionally acted as a proliferation-inhibitor. Additionally, TPTEP1 suppressed AML cell growth by inactivating c-Jun N-terminal kinase (JNK)/c-JUN signaling pathway. MicroRNA (MiR)-1303, as an oncogene, was predicted and validated as a target of c-JUN in AML cells. Also, TPTEP1 interacted with miR-1303 and they were mutually silenced by each other in AML cells. Furthermore, the effect of TPTEP1 overexpression on AML cell proliferation was counteracted under miR-1303 upregulation.
Our findings unmasked a feedback loop of TPTEP1/JNK/c-JUN/miR-1303 axis in AML cells, suggesting TPTEP1 and miR-1303 as potential targets for developing therapeutic strategies for AML patients.
非编码RNA（ncRNAs）已被确定为癌症发病机制和发展过程中的关键调节因子。然而，大多数ncRNAs在急性髓系白血病（AML）中尚未得到研究。
通过定量实时聚合酶链反应（qRT-PCR）或蛋白质免疫印迹法评估基因表达。进行功能试验以评估AML细胞中的细胞过程。通过一系列机制试验验证基因之间的关系。
张力蛋白同源性假基因1跨膜磷酸酶（TPTEP1）在AML细胞中显著下调，并且在功能上作为增殖抑制剂。此外，TPTEP1通过使c-Jun氨基末端激酶（JNK）/c-JUN信号通路失活来抑制AML细胞生长。微小RNA（MiR）-1303作为一种癌基因，在AML细胞中被预测并验证为c-JUN的靶标。此外，TPTEP1与miR-1303相互作用，并且它们在AML细胞中相互沉默。此外，在miR-1303上调的情况下，TPTEP1过表达对AML细胞增殖的影响被抵消。
我们的研究结果揭示了AML细胞中TPTEP1/JNK/c-JUN/miR-1303轴的反馈回路，表明TPTEP1和miR-1303作为开发AML患者治疗策略的潜在靶点。
