【摘要】 目的 探讨长链非编码RNA(lncRNA)钾离子电压门控通道亚家族Q成员1重叠转录本1(KCNQ1OT1)通过调控微小RNA-1179(miR-1179)/性别决定区Y框蛋白12(SOX12)轴影响急性髓系白血病(AML)细胞增殖和凋亡的机制。方法 将K562细胞分为NC组、sh-NC组、shKCNQ1OT1组、miR-NC组、miR-1179 mimics组、sh-KCNQ1OT1+anti-NC组、sh-KCNQ1OT1+antimiR-1179组、miR-1179 mimics+pc-NC组，miR-1179 mimics+pc-SOX12组;采用逆转录-聚合酶链式反应(RT-PCR)检测AML患者和非AML患者单核细胞及AML细胞中KCNQ1OT1、miR-1179和SOX12 mRNA的表达水平;验证miR-1179与KCNQ1OT1和SOX12的靶向关系。检测KCNQ1OT1、miR-1179和SOX12 mRNA表达水平、细胞增殖、凋亡、迁移、侵袭、CXCL-2和CXCL-8水平、SOX12、增殖细胞核抗原(PCNA)、E-cadherin、cleaved caspase-3、N-cadherin和vimentin蛋白表达水平。结果与NC组和sh-NC组比较，sh-KCNQ1OT1组K562细胞miR-1179表达水平、凋亡率、cleaved caspase-3和E-cadherin蛋白表达水平升高，KCNQ1OT1和SOX12 mRNA表达水平、细胞活力、克隆形成率、划痕愈合率、侵袭细胞数量、CXCL-2和CXCL-8水平、N-cadherin、vimentin、PCNA和SOX12蛋白表达水平降低;与miR-NC组比较，miR-1179 mimics组K562细胞miR-1179表达、凋亡率、cleaved caspase-3和E-cadherin蛋白表达水平升高，SOX12 mRNA表达水平、细胞活力、克隆形成率、划痕愈合率、侵袭细胞数量、CXCL-2和CXCL-8水平、N-cadherin、PCNA、vimentin和SOX12蛋白表达水平降低(P<0.05)。结论 沉默lncRNA KCNQ1OT1可通过上调miR-1179表达、靶向抑制SOX12转录，进而促进K562细胞凋亡，降低细胞活力、克隆形成率、划痕愈合率及侵袭细胞数量，抑制细胞上皮间质转化和免疫逃逸。更多还原

【Abstract】 Objective To explore the mechanism by which long non-coding RNA( lncRNA)potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1( KCNQ1 OT1) affects the proliferation and apoptosis of acute myeloid leukemia( AML) cells through regulating microRNA-1179( miR-1179)/sex-determining region Y-box protein 12( SOX12) axis. Methods K562 cells were divided into NC group,sh-NC group,sh-KCNQ1 OT1 group,miR-NC group,miR-1179 mimics group,shKCNQ1 OT1 + anti-NC group,sh-KCNQ1 OT1 + anti-miR-1179 group,miR-1179 mimics + pc-NC group and miR-1179 mimics + pc-SOX12 group. Reverse transcription-polymerase chain reaction( RT-PCR) was used to detect monocytes in both AML and non-AML patients,and the expression levels of KCNQ1 OT1,miR-1179 and SOX12 mRNA in AML cells. The targeting relationship between miR-1179 and KCNQ1 OT1 and SOX12 was verified. The expression levels of KCNQ1 OT1,miR-1179 and SOX12 mRNA,cell proliferation,apoptosis,migration,invasion,CXCL-2 and CXCL-8 levels and the expression levels of SOX12,proliferating cell nuclear antigen( PCNA),E-cadherin,cleaved caspase-3,N-cadherin and vimentin proteins were detected. Results Compared with NC group and sh-NC group,the expression level of miR-1179,apoptosis rate,cleaved caspase-3 and E-cadherin protein expression levels were increased in sh-KCNQ1 OT1 group of K562 cells,while the expression levels of KCNQ1 OT1 and SOX12 mRNA,cell viability,colony formation rate,scratch healing rate,number of invasive cells,CXCL-2 and CXCL-8 levels,N-cadherin,vimentin,PCNA and SOX12 protein expression levels were decreased; compared with miR-NC group,the expression level of miR-1179,apoptosis rate,cleaved caspase-3 and E-cadherin protein expression were increased in miR-1179 mimics group of K562 cells,while the expression level of SOX12 mRNA,cell viability,colony formation rate,scratch healing rate,number of invasive cells,CXCL-2 and CXCL-8 levels,N-cadherin,PCNA,vimentin and SOX12 protein expression levels were decreased( P <0. 05). Conclusion Silencing lncRNA KCNQ1 OT1 can promote the apoptosis of K562 cells,reduce cell viability,colony formation rate,scratch healing rate and the number of invasive cells,and inhibit cell epithelial-mesenchymal transition and immune escape by up-regulating the expression of miR-1179 and targeting inhibition of SOX12 transcription.更多还原