摘要
目的:探讨长链非编码RNA LINC00987在抗肿瘤药物诱导的急性髓系白血病(acute myeloid leukemia,AML)细胞凋亡中的作用及分子机制。方法:通过RT-qPCR检测AML中的LINC00987表达水平。构建稳定敲减LINC00987基因的Molm13细胞(shLINC00987),通过Annexin V/PI检测LINC00987低表达对阿糖胞苷诱导AML细胞凋亡的影响。对LINC00987共表达基因进行信号通路富集,分析LINC00987的表达对细胞色素家族基因的影响。结果:与健康对照组相比,lncRNA LINC00987在AML细胞系和AML病人标本中均显著降低,而在抗AML治疗后缓解组中高表达;此外,低表达LINC00987与AML患者预后不良有关。抗肿瘤药物阿糖胞苷、阿霉素、三氧化二砷和维奈托克可显著诱导AML细胞系Molm13和MV411的LINC00987表达。下调LINC00987的表达可抑制阿糖胞苷诱导的Molm13细胞凋亡。进一步研究发现,LINC00987共表达基因可富集于细胞色素P450(cytochrome,P450,CYP450)介导的氧化应激通路/网络,且LINC00987的表达与CYP450家族基因CYP11B1、CYP2U1和CYP2C9的表达水平呈正相关。下调LINC00987的表达则可抑制阿糖胞苷诱导的CYP11B1、CYP2U1和CYP2C9的mRNA表达。结论:LINC00987可以作为AML的预后标志物,其可能通过CYP450介导的氧化应激途径促进阿糖胞苷诱导的AML细胞凋亡。
AIM:To investigate the role and molecular mechanism of long noncoding RNA LINC00987 in the apoptosis of acute myeloid leukemia(AML)cells induced by antitumor drugs.METHODS:The LINC00987 expression in AML was detected by RT-qPCR.The Molm13 cells with stable knockdown of LINC00987 gene(shLINC00987)were constructed,and the effect of low LINC00987 expression on the apoptosis of AML cells induced by cytarabine was detected by annexin V/PI staining.Signaling pathway enrichment of LINC00987-coexpressed genes was performed to analyze the effect of LINC00987 expression on cytochrome family genes.RESULTS:Compared with healthy individual group,the expression of LINC00987 was significantly down-regulated in AML cell lines and patients,but highly up-regulated in the complete remission group after anti-AML treatment.In addition,low LINC00987 expression was associated with poor prognosis among the patients with AML.The LINC00987 expression in AML cell lines Molm13 and MV411 was significantly induced by antitumor drugs such as cytarabine,doxorubicin,arsenic trioxide,and venetoclax.Meanwhile,LINC00987 down-regulation could inhibit the apoptosis of Molm13 cells induced by cytarabine.The LINC00987-coexpressed genes were enriched in cytochrome P450(CYP450)-mediated oxidative stress pathways,and the LINC00987 expression was positively correlated with the expression of CYP450 family genes CYP11B1,CYP2U1 and CYP2C9.Down-regulation of LINC00987 could inhibit the mRNA expression of CYP11B1,CYP2U1 and CYP2C9 induced by cytarabine.CONCLU⁃SION:Long noncoding RNA LINC00987 can be used as a prognostic marker for AML and may promote cytarabine-in-duced AML cell apoptosis through CYP450-mediated oxidative stress pathways.
作者
杨彭月
刘暄
王艳
徐玲
李扬秋
余锡宝
YANG Pengyue;LIU Xuan;WANG Yan;XU Ling;LI Yangqiu;YU Xibao(Institute of Hematology,School of Medicine,Key Laboratory of Regenerative Medicine of Ministry of Education,Jinan University,Guangzhou 510632,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2024年第2期265-273,共9页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.82200167)
广东省基础与应用基础研究基金资助项目(No.2021A1515110140)。