Ma Zhong-Liang, Zhang Bing-Jie, Wang D Tao, Li Xue, Wei Jia-Li, Zhao Bo-Tao, Jin Yan, Li Yan-Li, Jin You-Xin
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Oncotarget. 2015 Aug 21;6(24):20111-20. doi: 10.18632/oncotarget.3933.
Tanshinone is the liposoluble constituent of Salia miltiorrhiza, a root used in traditional herbal medicine which is known to possess certain health benefits. Although it is known that tanshinones, including tanshinone I (T1), tanshinone IIA (T2A), and cryptotanshinone (CT), can inhibit the growth of lung cancer cells in vitro, the mechanism under which they act is still unclear. AURKA, an oncogene, encodes a serine-threonine kinase which regulates mitotic processes in mammalian cells. Here, we reported that tanshinones mediate AURKA suppression partly through up-regulating the expression of miR-32. We found that tanshinones could inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression, thus performing an antineoplastic function in non-small cell lung cancer (NSCLC). Additionally, we demonstrated that tanshinones attained these effects in part by down-regulating AURKA, corroborating previous reports. Our results showed that in NSCLC, similar effects were obtained with knock-down of the AURKA gene by siRNA. We also verified that AURKA was the direct target of miR-32. Collectively, our results demonstrated that tanshinones could inhibit NSCLC by suppressing AURKA via up-regulating the expressions of miR-32 and other related miRNAs.
丹参酮是丹参根中的脂溶性成分,丹参根是一种传统草药,已知具有一定的健康益处。尽管已知丹参酮,包括丹参酮 I(T1)、丹参酮 IIA(T2A)和隐丹参酮(CT),在体外可抑制肺癌细胞的生长,但其作用机制仍不清楚。AURKA 是一种癌基因,编码一种丝氨酸 - 苏氨酸激酶,可调节哺乳动物细胞中的有丝分裂过程。在此,我们报告丹参酮部分通过上调 miR - 32 的表达介导 AURKA 的抑制。我们发现丹参酮可抑制细胞增殖、促进细胞凋亡并阻碍细胞周期进程,从而在非小细胞肺癌(NSCLC)中发挥抗肿瘤作用。此外,我们证明丹参酮部分通过下调 AURKA 达到这些效果,这与先前的报道一致。我们的结果表明,在 NSCLC 中,通过 siRNA 敲低 AURKA 基因可获得类似的效果。我们还证实 AURKA 是 miR - 32 的直接靶点。总体而言,我们的结果表明丹参酮可通过上调 miR - 32 和其他相关 miRNA 的表达抑制 AURKA,从而抑制 NSCLC。