长链非编码 RNA HOTAIR 与 SP1 介导的 PDK1 抑制作用的串扰促进β-榄香烯抑制肝癌细胞增殖。
Crosstalk of LncRNA HOTAIR and SP1-mediated repression of PDK1 contributes to β-Elemene-inhibited proliferation of hepatocellular carcinoma cells.
机构信息
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China.
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China.
出版信息
J Ethnopharmacol. 2022 Jan 30;283:114456. doi: 10.1016/j.jep.2021.114456. Epub 2021 Jul 29.
ETHNOPHARMACOLOGICAL RELEVANCE
Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. β-Elemene refers to a natural Curcuma wenyujin-derived single molecular entity, which exhibits various biological activities, and is especially well-known for it's antitumor properties.
AIM OF THE RESEARCH
LncRNA HOTAIR, SP1, and PDK1 have displayed oncogenic roles in many tumors, participating in the initiation and progression of cancers by mediating multiple signaling pathways. However, there are only a few reports about their roles and mutual relationship in the growth of HCC cells. Therefore, this study aimed to investigate the expression of LncRNA HOTAIR, SP1, and PDK1 and their interaction with β-Elemene in HCC cells.
MATERIALS AND METHODS
MTT, a Colony formation assay, and flow cytometry were employed to evaluate the growth of HCC and LO2 cells under β-Elemene. LncRNA HOTAIR, SP1 and PDK1 plasmids were transfected into HCC cells by a transient transfection assay, and the expression and interaction of LncRNA HOTAIR, SP1 and PDK1 were assessed via qRT-PCR and western blotting.
RESULTS
β-Elemene suppressed HCC cell growth through the downregulation of LncRNA HOTAIR, SP1 and PDK1. The results demonstrated a reciprocal interaction among LncRNA HOTAIR, SP1 and PDK1. Exogenous overexpression LncRNA HOTAIR or SP1 eliminated the suppressive effects of β-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or LncRNA HOTAIR prevented β-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and LncRNA HOTAIR expression by β-Elemene.
CONCLUSION
β-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.
民族药理学相关性
肝细胞癌（HCC）是一种肝脏恶性肿瘤，缺乏有效治疗方法，预后较差。β-榄香烯是一种天然莪术衍生的单一分子实体，具有多种生物学活性，尤其以其抗肿瘤特性而闻名。
研究目的
长链非编码 RNA HOTAIR、SP1 和 PDK1 在许多肿瘤中表现出致癌作用，通过介导多种信号通路参与癌症的发生和发展。然而，关于它们在 HCC 细胞生长中的作用及其相互关系的报道较少。因此，本研究旨在探讨 HCC 细胞中 LncRNA HOTAIR、SP1 和 PDK1 的表达及其与β-榄香烯的相互作用。
材料和方法
采用 MTT、集落形成实验和流式细胞术评估β-榄香烯对 HCC 和 LO2 细胞生长的影响。通过瞬时转染实验将 LncRNA HOTAIR、SP1 和 PDK1 质粒转染入 HCC 细胞，通过 qRT-PCR 和 Western blot 评估 LncRNA HOTAIR、SP1 和 PDK1 的表达和相互作用。
结果
β-榄香烯通过下调 LncRNA HOTAIR、SP1 和 PDK1 抑制 HCC 细胞生长。结果表明 LncRNA HOTAIR、SP1 和 PDK1 之间存在相互作用。外源性过表达 LncRNA HOTAIR 或 SP1 消除了β-榄香烯对它们的抑制作用，两者均调节 HCC 细胞中 PDK1 的表达。此外，外源性过表达 SP1 或 LncRNA HOTAIR 可阻止β-榄香烯抑制 PDK1 的蛋白水平表达，而过表达 PDK1 虽然对 SP1 没有影响，但仍可减弱β-榄香烯对细胞生长和 LncRNA HOTAIR 表达的抑制作用。
结论
β-榄香烯通过调节 LncRNA HOTAIR、SP1、PDK1 及其相互作用抑制 HCC 细胞增殖。
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