长链非编码RNA LINC00987通过细胞色素P450途径促进AML细胞凋亡的机制研究OA北大核心CSTPCD

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 ef-fect of LINC00987 expression on cytochrome family genes.RESULTS:Compared with healthy individual group,the ex-pression 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 prog-nosis 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.