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通过上调硬脂酰辅酶A去饱和酶(SCD)保护急性髓系白血病细胞免受铁死亡细胞死亡

Protects Acute Myeloid Leukemia Cells from Ferroptotic Cell Death by Upregulating SCD.

作者信息

Long Fei, Lin Zhi, Long Qinpeng, Lu Zhixing, Zhu Kaiyu, Zhao Mingyi, Yang Minghua

机构信息

Department of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China.

Postdoctoral Research Station of Basic Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, China.

出版信息

Cancers (Basel). 2023 Jan 11;15(2):459. doi: 10.3390/cancers15020459.

DOI:10.3390/cancers15020459
PMID:36672408
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9857113/
Abstract

Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that was significantly upregulated in AML patients and AML cells. Moreover, the expression of was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the knockdown repressed the tumor growth of AML in vivo. In conclusion, protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that may be a potential therapeutic target for AML.

摘要

环状RNA(circRNAs)已被证明与血液系统恶性肿瘤的发生发展及治疗反应密切相关。然而,circRNAs在急性髓系白血病(AML)中的生物学功能和临床意义仍 largely未知。对circRNA微阵列数据集进行分析以筛选AML患者中差异表达的circRNAs。发现[具体circRNA名称]在AML患者和AML细胞中显著上调。此外,[具体circRNA名称]的表达与AML患者的分期相关,并且对诊断AML具有高敏感性和特异性。沉默[具体circRNA名称]可抑制AML细胞增殖并诱导细胞周期停滞。重要的是,[具体circRNA名称]的缺失显著增加了AML细胞中的铁死亡,并增强了RSL3诱导的铁死亡。机制上,[具体circRNA名称]可能通过作为miRNA海绵上调硬脂酰辅酶A去饱和酶1(SCD)的表达。最后,[具体circRNA名称]敲低抑制了AML在体内的肿瘤生长。总之,[具体circRNA名称]通过上调SCD保护AML细胞免受铁死亡并促进增殖,因此表明[具体circRNA名称]可能是AML的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/198a7779c7d1/cancers-15-00459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/9437d56857d0/cancers-15-00459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/8f0b102a18ce/cancers-15-00459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/a4b66d8c6aa3/cancers-15-00459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/9fc8b69729db/cancers-15-00459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/301297773f25/cancers-15-00459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/198a7779c7d1/cancers-15-00459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/9437d56857d0/cancers-15-00459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/8f0b102a18ce/cancers-15-00459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/a4b66d8c6aa3/cancers-15-00459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/9fc8b69729db/cancers-15-00459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/301297773f25/cancers-15-00459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2076/9857113/198a7779c7d1/cancers-15-00459-g006.jpg

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