Laboratory of Tumor Biology, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Medical Oncology, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, China.
J Cell Mol Med. 2019 Nov;23(11):7749-7761. doi: 10.1111/jcmm.14649. Epub 2019 Sep 1.
Solamargine (SM) has been shown to have anti-cancer properties. However, the underlying mechanism involved remains undetermined. We showed that SM inhibited the growth of non-small cell lung cancer (NSCLC) cells, which was enhanced in cells with silencing of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), while it overcame by overexpression of HOTAIR. In addition, SM increased the expression of miR-214-3p and inhibited 3-phosphoinositide-dependent protein kinase-1 (PDPK1) gene expression, which was strengthened by miR-214-3p mimics. Intriguingly, HOTAIR could directly bind to miR-214-3p and sequestered miR-214-3p from the target gene PDPK1. Intriguingly, overexpression of PDPK1 overcame the effects of SM on miR-214-3p expressions and neutralized the SM-inhibited cell growth. Similar results were observed in vivo. In summary, our results showed that SM-inhibited NSCLC cell growth through the reciprocal interaction between HOTAIR and miR-214-3p, which ultimately suppressed PDPK1 gene expression. HOTAIR effectively acted as a competing endogenous RNA (ceRNA) to stimulate the expression of target gene PDPK1. These complex interactions and feedback mechanisms contribute to the overall effect of SM. This unveils a novel molecular mechanism underlying the anti-cancer effect of SM in human lung cancer.
索拉马林（SM）已被证明具有抗癌特性。然而，其涉及的潜在机制仍未确定。我们表明，SM 抑制非小细胞肺癌（NSCLC）细胞的生长，而在沉默长链非编码 RNA（lncRNA）HOX 转录反义 RNA（HOTAIR）的细胞中，这种抑制作用增强，而过表达 HOTAIR 则克服了这种抑制作用。此外，SM 增加了 miR-214-3p 的表达，并抑制了 3-磷酸肌醇依赖性蛋白激酶-1（PDPK1）基因的表达，而 miR-214-3p 模拟物则增强了这种表达。有趣的是，HOTAIR 可以直接与 miR-214-3p 结合，并将 miR-214-3p 从靶基因 PDPK1 中隔离出来。有趣的是，PDPK1 的过表达克服了 SM 对 miR-214-3p 表达的影响，并中和了 SM 抑制的细胞生长。在体内也观察到了类似的结果。总之，我们的研究结果表明，SM 通过 HOTAIR 和 miR-214-3p 的相互作用抑制 NSCLC 细胞生长，从而最终抑制 PDPK1 基因的表达。HOTAIR 有效地作为竞争性内源性 RNA（ceRNA）刺激靶基因 PDPK1 的表达。这些复杂的相互作用和反馈机制促成了 SM 的整体效应。这揭示了 SM 在人类肺癌中抗癌作用的新分子机制。
