LncRNA KCNQ1OT1 controls cell proliferation, differentiation and apoptosis by sponging miR-326 to regulate c-Myc expression in acute myeloid leukemia
LncRNA KCNQ1OT1 controls cell proliferation, differentiation and apoptosis by sponging miR-326 to regulate c-Myc expression in acute myeloid leukemia
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DOI：
10.4149/neo_2018_181215n972
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发表时间：
2020-01-01
期刊：
影响因子：
3
通讯作者：
Cheng, H.
中科院分区：
文献类型：
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作者：
Cheng, P.;Lu, P.;Cheng, H.
长链非编码RNA（lncRNA）在急性髓细胞白血病（AML）的发生、发展和治疗中起重要作用。然而，lncRNA钾电压门控通道亚家族Q成员1重叠转录本1（KCNQ 1 OT 1）在AML进展中的作用及其机制在很大程度上仍然未知。采用实时定量聚合酶链反应（real-time polymerase chain reaction，RT-PCR）和western blot分别检测KCNQ 1 OT 1、microRNA-326（miR-326）和c-Myc的表达。将佛波醇肉豆蔻酸酯乙酸酯（PMA）用于细胞分化。MTT法、流式细胞术和qRT-PCR分别检测细胞增殖、凋亡和分化。通过荧光素酶活性、RNA免疫沉淀或RNA pull-down分析探讨miR-326与KCNQ 1 OT 1或c-Myc的相互作用。我们发现，KCNQ 1 OT 1的表达在AML样品中与对照相比增强。KCNQ 1 OT 1敲低抑制细胞增殖，但促进细胞凋亡和细胞分化。KCNQ 1 OT 1是miR-326的诱饵，c-Myc是miR-326的靶点。KCNQ 1 OT 1通过吸收miR-326调控AML细胞增殖、凋亡和分化。此外，miR-326的过表达通过靶向AML细胞中的c-Myc抑制增殖，但促进凋亡和PMA诱导的分化。此外，c-Myc蛋白水平被KCNQ 1 OT 1干扰抑制，并被miR-326废除拯救。我们的数据显示，KCNQ 1 OT 1通过作为miR-326的竞争性内源性RNA（ceRNA）调节c-Myc来调节AML细胞的增殖、分化和凋亡，为AML治疗提供了新的途径。
Long noncoding RNAs (lncRNAs) have been reported to play essential roles in development and treatment of acute myeloid leukemia (AML). However, the role of lncRNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) in AML progression and its mechanism remain largely unknown. The expressions of KCNQ1OT1, microRNA-326 (miR-326) and c-Myc were measured by quantitative real-time polymerase chain reaction and western blot, respectively. Phorbol myristate acetate ( PM A) was used for cell differentiation. Cell proliferation, apoptosis and differentiation were measured by MTT assay, flow cytometry and qRT-PCR, respectively. The interaction between miR-326 and KCNQ1OT1 or c-Myc was explored by luciferase activity, RNA immunoprecipitation or RNA pull-down assay. We found that the expression of KCNQ1OT1 was enhanced in AML samples compared with control. KCNQ1OT1 knockdown inhibited cell proliferation but promoted apoptosis and cell differentiation. KCNQ1OT1 was a decoy of miR-326 and c-Myc was a target of miR-326. KCNQ1OT1 regulated AML cell proliferation, apoptosis and differentiation by sponging miR-326. Moreover, overexpression of miR-326 suppressed proliferation but promoted apoptosis and PMA-induced differentiation by targeting c-Myc in AML cells. Besides, c-Myc protein level was suppressed by KCNQ1OT1 interference and rescued by miR-326 abrogation. Our data showed that KCNQ1OT1 regulates proliferation, differentiation and apoptosis in AML cells by acting as a competing endogenous RNA (ceRNA) for miR-326 to regulate c-Myc, providing a novel avenue for AML treatment.