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

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.

SUBMITTER: Zhuang Q

PROVIDER: S-EPMC8060808 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFerroptosis is a newly discovered type of programmed cell death that participates in the biological processes of various cancers. However, the mechanism by which ferroptosis modulates acute myeloid leukemia (AML) remains unclear. This study aimed to investigate the role of ferroptosis-related long non-coding RNAs (lncRNAs) in AML and establish a corresponding prognostic model.MethodsRNA-sequencing data and clinicopathological characteristics were obtained from The Cancer Genome Atlas database, and ferroptosis-related genes were obtained from the FerrDb database. The "limma" R package, Cox regression, and the least absolute shrinkage and selection operator were used to determine the ferroptosis-related lncRNA signature with the lowest Akaike information criteria (AIC). The risk score of ferroptosis-related lncRNAs was calculated and patients with AML were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier curve and Cox regression were used to evaluate the prognostic value of the risk score. Finally, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological functions of the ferroptosis-related lncRNAs.ResultsSeven ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan-Meier and Cox regression analyses confirmed that risk scores were independent prognostic predictors of AML in both the training and validation groups (All P < 0.05). In addition, the area under the curve (AUC) analysis confirmed that the signatures had a good predictive ability for the prognosis of AML. GSEA and ssGSEA showed that the seven ferroptosis-related lncRNAs were related to glutathione metabolism and tumor immunity.ConclusionsIn this study, seven novel ferroptosis-related lncRNA signatures (AP001266.2, AC133961.1, AF064858.3, AC007383.2, AC008906.1, AC026771.1, and KIF26B-AS1) were established. These signatures were shown to accurately predict the prognosis of AML, which would provide new insights into strategies for the development of new AML therapies.

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

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