Circular RNA HIPK3 exerts oncogenic properties through suppression of miR-124 in lung cancer.
Circular RNA HIPK3 exerts oncogenic properties through suppression of miR-124 in lung cancer.
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DOI：
10.1016/j.bbrc.2018.10.087
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发表时间：
2018-11
影响因子：
3.1
通讯作者：
Hanqing Yu;Yu Chen;P. Jiang
中科院分区：
文献类型：
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作者：
Hanqing Yu;Yu Chen;P. Jiang
本研究检测了环状RNAHIPK3（circHIPK3）在人肺癌中的表达和潜在功能。我们的结果表明，与肺上皮细胞中的低水平相比，circHIPK3 表达在已建立的（A549 系）和原代人肺癌细胞中上调。 siRNA介导的circHIPK3沉默有效抑制肺癌细胞的存活和增殖，但诱导显着的细胞凋亡激活。相反，通过慢病毒构建体强制过度表达circHIPK3可促进肺癌细胞的存活和增殖。CircHIPK3作为microRNA-124（miR-124）海绵体并调节肺癌细胞中miR-124 mRNA靶标（包括SphK1、CDK4和STAT3）的表达。 miR-124抑制剂的转染显着抑制circHIPK3siRNA诱导的肺癌细胞死亡和凋亡。最后，我们发现 circHIPK3 水平在人肺癌组织中上调，与 miR-124 下调相关。 miR-124 靶标（SphK1、STAT3 和 CDK4）在肺癌组织中表达上调。我们共同提出，circHIPK3 可能通过海绵 miR-124 促进肺癌细胞进展。这些观察结果表明一种可能涉及 circHIPK3-miR-124 通路的肺癌新治疗策略。
The current study tested the expression and potential functions ofcircular RNAHIPK3(circHIPK3) in human lung cancer. Our results show thatcircHIPK3expression is upregulated in established (A549 line) and primary human lung cancer cells, when compared to its low level in the lung epithelial cells. siRNA-mediated silencing ofcircHIPK3potently inhibited survival and proliferation of lung cancer cells, but inducing significant apoptosis activation. Contrarily, forced overexpression ofcircHIPK3by a lentiviral construct promoted lung cancer cell survival and proliferation.CircHIPK3acted as amicroRNA-124(miR-124) sponger and regulated the expression ofmiR-124 mRNA targets, includingSphK1,CDK4andSTAT3, in lung cancer cells. Transfection ofmiR-124inhibitor significantly inhibitedcircHIPK3siRNA-induced lung cancer cell death and apoptosis. At last, we show thatcircHIPK3levels are upregulated in human lung cancer tissues, correlated withmiR-124downregulation. ThemiR-124targets (SphK1,STAT3andCDK4) are upregulated in lung cancer tissues. Together, we propose thatcircHIPK3promotes lung cancer cell progression possibly by spongingmiR-124. These observations indicate a possible novel therapeutic strategy involvingcircHIPK3-miR-124pathway against lung cancer.