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长链非编码 RNA LINC00460 通过调节 miR-320b/PBX3 轴在急性髓系白血病中作为潜在的生物标志物和癌基因。

Long non‑coding RNA LINC00460 serves as a potential biomarker and oncogene via regulation of the miR‑320b/PBX3 axis in acute myeloid leukemia.

机构信息

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.

Department of Experimental Center, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.

出版信息

Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12074. Epub 2021 Apr 13.

Abstract

Long non‑coding RNA 00460 (LINC00460) has been reported to be involved in the tumorigenesis of various cancer types. However, the function of LINC00460 in acute myeloid leukemia (AML) remains elusive. Therefore, the present study aimed to investigate the role of LINC00460 in AML. The expression of LINC00460 in the serum of 80 diagnosed patients with AML and 67 healthy controls was measured via reverse transcription‑quantitative polymerase chain reaction, and the results were compared with clinical features and patient outcomes. The expression of LINC00460 in 45 patients with cytogenetically normal‑AML (CN‑AML) was also assayed. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity and specificity of serum LINC00460. In addition, the effects of LINC00460 on the viability, cell cycle distribution and apoptosis of AML cells were investigated. Bioinformatics tools were used to identify the possible mechanisms of how LINC00460 affects AML cells. It was found that the expression of LINC00460 was significantly upregulated in the serum of patients with AML and those with CN‑AML. Higher expression of serum LINC00460 was positively associated with French‑American‑British classification and cytogenetics. Furthermore, ROC curve analyses demonstrated that serum LINC00460 could differentiate patients with AML from healthy individuals with an area under the curve of 0.8488 (95% CI, 0.7697‑0.9279). The serum LINC00460 expression was also significantly decreased when the patients achieved complete remission. Kaplan‑Meier analysis indicated that patients with high serum LINC00460 expression had a shorter overall survival time compared with the low serum LINC00460 expression group. Knockdown of LINC00460 inhibited viability, while inducing cell cycle arrest and apoptosis in AML cells. LINC00460 was also a decoy of microRNA (miR)‑320b, which can further inhibit the expression of PBX homeobox 3 (PBX3). Collectively, the results suggested that LINC00460 may be applied as a potential diagnostic and prognostic biomarker for patients with AML. It was identified that LINC00460 may exert its effects, at least partly, via the miR‑320b/PBX3 axis in AML.

摘要

长链非编码 RNA 00460(LINC00460)已被报道参与多种癌症类型的肿瘤发生。然而,LINC00460 在急性髓系白血病(AML)中的功能仍然难以捉摸。因此,本研究旨在探讨 LINC00460 在 AML 中的作用。通过逆转录-定量聚合酶链反应测量了 80 名确诊的 AML 患者和 67 名健康对照者血清中的 LINC00460 表达,并将结果与临床特征和患者结局进行了比较。还检测了 45 例核型正常 AML(CN-AML)患者的 LINC00460 表达。绘制受试者工作特征(ROC)曲线以评估血清 LINC00460 的敏感性和特异性。此外,还研究了 LINC00460 对 AML 细胞活力、细胞周期分布和凋亡的影响。生物信息学工具用于确定 LINC00460 影响 AML 细胞的可能机制。结果发现,AML 患者和 CN-AML 患者血清中的 LINC00460 表达明显上调。血清 LINC00460 高表达与 French-American-British 分类和细胞遗传学呈正相关。此外,ROC 曲线分析表明,血清 LINC00460 可将 AML 患者与健康个体区分开来,曲线下面积为 0.8488(95%CI,0.7697-0.9279)。当患者达到完全缓解时,血清 LINC00460 表达也显著降低。Kaplan-Meier 分析表明,血清 LINC00460 高表达的患者总生存期短于血清 LINC00460 低表达组。敲低 LINC00460 抑制了 AML 细胞的活力,同时诱导了细胞周期停滞和凋亡。LINC00460 也是 microRNA(miR)-320b 的诱饵,它可以进一步抑制 PBX 同源盒 3(PBX3)的表达。总之,这些结果表明 LINC00460 可作为 AML 患者潜在的诊断和预后生物标志物。确定 LINC00460 至少部分通过 miR-320b/PBX3 轴在 AML 中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0486/8060808/ca725bb3028d/mmr-23-06-12074-g00.jpg

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