Oncogenic lncRNA FAM215A promotes the malignant cell phenotypes of acute myeloid leukemia (AML) cell lines

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-01-02 DOI:10.1007/s10735-023-10174-1

Lin Li, Liuyan Xin, Xiang Yang, Zhengrong Zou

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Abstract

Acute myeloid leukemia (AML) is a form of blood cancer that arise as a result of clonal proliferation of malignant myeloid precursors acquiring genetic abnormalities. Primary resistance to initial treatment and disease recurrence continues to be huge challenge in treating AML. Herein, GSE114868 was analyzed for differentially-expressed lncRNAs between AML patients’ mononucleated cells and healthy normal control mononucleated cells and 191 lncRNAs were significantly deregulated in AML patients’ mononucleated cells. The correlation between candidate lncRNAs and AML patients’ overall survival was analyzed and 6 lncRNAs, including MIR181A1HG, TRAF3IP2-AS1, STARD4-AS1, E2F3-IT1, FAM215A, and HHIP-AS1 were dramatically linked to AML patients’ OS. Using a Cox proportional-hazards model, we identified risk factors and found FAM215A as a risk factor for AML patients’ prognosis. The expression level of FAM215A showed to be upregulated within blood samples and cells. Genes correlated with FAM215A were correlated to cell division, modulation of cell apoptosis, and modulation of programmed cell death. FAM215A knockdown inhibited AML cell viability, elicited G0/G1-phase arrest of cell cycle, enhanced cell apoptosis, increased proapoptotic Bax and cleaved-caspase3 levels, and decreased antiapoptotic Bcl2. FAM215A overexpression exerted opposite effects on AML cells. Conclusively, FAM215A serves as an oncogenic lncRNA in AML, promoting cell viability, relieving cell cycle arrest, and suppressing cell apoptosis. FAM215A might be un underlying biological prognostic marker and therapeutic target for AML.

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致癌 lncRNA FAM215A 可促进急性髓性白血病（AML）细胞系的恶性细胞表型

急性髓细胞白血病（AML）是一种血癌，是恶性髓细胞前体获得基因异常后克隆性增殖的结果。初治耐药和疾病复发仍然是治疗 AML 的巨大挑战。在此，GSE114868分析了AML患者单核细胞与健康正常对照单核细胞之间差异表达的lncRNA，结果发现191个lncRNA在AML患者单核细胞中显著失调。分析了候选lncRNAs与AML患者总生存期的相关性，结果显示，MIR181A1HG、TRAF3IP2-AS1、STARD4-AS1、E2F3-IT1、FAM215A和HHIP-AS1等6个lncRNAs与AML患者的OS显著相关。我们利用 Cox 比例危险模型确定了风险因素，并发现 FAM215A 是影响 AML 患者预后的一个风险因素。在血液样本和细胞中，FAM215A的表达水平呈上调趋势。与FAM215A相关的基因与细胞分裂、细胞凋亡调节和细胞程序性死亡调节相关。FAM215A 基因敲除抑制了急性髓细胞白血病细胞的活力，引起细胞周期 G0/G1 期停滞，增强了细胞凋亡，提高了促凋亡 Bax 和裂解-caspase3 的水平，降低了抗凋亡 Bcl2 的水平。FAM215A 的过表达对 AML 细胞产生了相反的影响。综上所述，FAM215A在AML中是一种致癌lncRNA，可促进细胞活力、缓解细胞周期停滞并抑制细胞凋亡。FAM215A可能是急性髓细胞性白血病的潜在生物学预后标志和治疗靶点。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.