Circ_0001946 Promotes the Development of Acute Myeloid Leukemia by Upregulating PDL1

IF 1.5 4区医学 Q3 HEMATOLOGY

Turkish Journal of Hematology Pub Date : 2023-08-31 DOI:10.4274/tjh.galenos.2023.2022.0484

Guohui Li, Conghui Zhu, Dan Qiao, Renan Chen

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引用次数: 1

Abstract

Objective: Circ_0001946 has been identified as an oncogenic factor, and the aim of this study was to explore the detailed roles and putative targets of circ_0001946 in acute myeloid leukemia (AML).

Materials and methods: Levels of circ_0001946 were examined in AML tissues and cells. Furthermore, the regulatory functions of circ_0001946 in AML were explored. The expression of circ_0001946 was evaluated in AML samples and a matched para-carcinoma control, as well as in AML cell lines and a human bone marrow stromal cell line using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was examined using a CCK-8 kit, and migration/invasion was measured by transwell assay. Furthermore, interactions between associated molecules were assessed using RNA pulldown, and the mRNA stability of the relevant gene was examined by mRNA stability assay.

Results: Our data indicated that circ_0001946 was upregulated in AML specimens/cells. Additionally, overexpression of circ_0001946 promoted the proliferation, migration, and invasion of AML cells and, vice versa, these biological processes were suppressed by knockdown of circ_0001946. Furthermore, PDL1 is a potential downstream molecule of circ_0001946 in AML and its stability was improved by circ_0001946. The expression of PDL1 was increased in AML specimens and positively correlated with circ_0001946 expression. Moreover, biological behavioral alterations in AML cells induced by oe-circ_0001946 were abrogated by sh-PDL1 and the effects of sh-circ_0001946 were enhanced by treatment with sh-PDL1.

Conclusion: Taken together, these data suggest that levels of circ_0001946 are elevated in AML and that circ_0001946 could promote the growth of AML cells. Furthermore, PDL1 is a novel downstream molecule of circ_0001946 in AML. Circ_0001946/PDL1 signaling may play crucial roles in tumor progression in AML and could be a novel candidate for targeted treatments for AML patients.

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Circ_0001946通过上调PDL1促进急性髓系白血病的发展

目的:Circ_0001946已被确定为一种致癌因子，本研究的目的是探讨Circ_0001946在急性髓性白血病(AML)中的详细作用和可能的靶点。材料和方法:检测AML组织和细胞中circ_0001946的水平。进一步探讨circ_0001946在AML中的调控功能。circ_0001946在AML样本和匹配的癌旁对照中，以及在AML细胞系和人骨髓基质细胞系中使用逆转录-定量聚合酶链反应进行表达评估。采用CCK-8试剂盒检测细胞增殖，transwell法检测细胞迁移/侵袭。此外，通过RNA pull - down评估相关分子之间的相互作用，并通过mRNA稳定性试验检测相关基因的mRNA稳定性。结果:我们的数据表明circ_0001946在AML标本/细胞中上调。此外，circ_0001946的过表达促进了AML细胞的增殖、迁移和侵袭，反之亦然，这些生物学过程被circ_0001946的敲低抑制。此外，PDL1是circ_0001946在AML中的潜在下游分子，circ_0001946提高了PDL1的稳定性。AML标本中PDL1表达升高，与circ_0001946表达呈正相关。此外，sh-PDL1消除了e-circ_0001946诱导的AML细胞的生物学行为改变，sh-PDL1增强了sh-circ_0001946的作用。结论:综上所述，这些数据表明circ_0001946水平在AML中升高，circ_0001946可以促进AML细胞的生长。此外，PDL1是AML中circ_0001946的一个新的下游分子。Circ_0001946/PDL1信号可能在AML的肿瘤进展中发挥关键作用，并可能成为AML患者靶向治疗的新候选药物。

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来源期刊

Turkish Journal of Hematology HEMATOLOGY-

CiteScore

2.90

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： The Turkish Journal of Hematology is published quarterly (March, June, September, and December) by the Turkish Society of Hematology. It is an independent, non-profit peer-reviewed international English-language periodical encompassing subjects relevant to hematology. The Editorial Board of The Turkish Journal of Hematology adheres to the principles of the World Association of Medical Editors (WAME), International Council of Medical Journal Editors (ICMJE), Committee on Publication Ethics (COPE), Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The aim of The Turkish Journal of Hematology is to publish original hematological research of the highest scientific quality and clinical relevance. Additionally, educational material, reviews on basic developments, editorial short notes, images in hematology, and letters from hematology specialists and clinicians covering their experience and comments on hematology and related medical fields as well as social subjects are published. As of December 2015, The Turkish Journal of Hematology does not accept case reports. Important new findings or data about interesting hematological cases may be submitted as a brief report.