LINC00221 抑制儿童急性淋巴细胞白血病的恶性程度。
LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia.
机构信息
Department of Hematology, Suzhou Dushuhu Public Hospital (Dushuhu Public Hospital Affiliated to Soochow University, The First Affiliated Hospital of Soochow University, Dushuhu Branch), Suzhou, Jiangsu 215000, China.
Department of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
出版信息
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20194070.
As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2.
作为儿童最常见的恶性疾病，儿童急性淋巴细胞白血病（ALL）是一种由累积的遗传改变引起的异质性疾病。长非编码 RNA（lncRNA）被报道为疾病的关键调节因子。GEPIA 数据库表明，长基因间非蛋白编码 RNA 221（LINC00221）在急性髓系白血病中明显下调。然而，其在 ALL 中的表达模式尚未揭示。本研究旨在研究 LINC00221 在 ALL 细胞中的作用。实时定量 PCR（qRT-PCR）定量检测 ALL 细胞中 LINC00221 的表达。通过 ki-67 免疫荧光染色、EdU、TUNEL、JC-1 和 caspase-3/8/9 活性测定来确定 LINC00221 在 ALL 中的功能。RNA 下拉和 Ago2-RNA 免疫沉淀（RIP）测定研究了 miR-152-3p 与 LINC00221 或三磷酸腺苷酶 sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2（ATP2A2）之间的相互作用。我们的研究表明 LINC00221 在 ALL 细胞中低表达。随后，验证 LINC00221 与 miR-152-3p 结合。此外，功能测定指出，LINC00221 过表达在 ALL 细胞中表现出抗增殖和促凋亡作用，这些作用可分别通过 miR-152-3p 的上调来逆转。随后，发现 LINC00221 通过海绵吸附 miR-152-3p 来调节 ATP2A2 的表达。此外，验证了 ATP2A2 参与调节 LINC00221 介导的 ALL 细胞增殖和凋亡。总之，LINC00221 通过海绵吸附 miR-152-3p 抑制 ALL 细胞增殖并促进 ALL 细胞凋亡，从而上调 ATP2A2。
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