Crosstalk of LncRNA HOTAIR and SP1-mediated repression of PDK1 contributes to β-Elemene-inhibited proliferation of hepatocellular carcinoma cells

作者：Wu, JingJing^*; Tang, XiaoJuan; Shi, Yao; Ma, ChangJu; Zhang, Hongyu; Zhang, Junhong; Lu, Yue; Wei, Jianan; Li, Li; Han, Ling^*

来源：Journal of Ethnopharmacology, 2022, 283: 114456.

DOI：10.1016/j.jep.2021.114456

• Hepatocellular carcinoma cells
• ?? -Elemene
• LncRNA HOTAIR
• SP1
• PDK1

Ethnopharmacological relevance: Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. ll-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 ll-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 ll-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: ll-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 over expression LncRNA HOTAIR or SP1 eliminated the suppressive effects of ll-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or LncRNA HOTAIR prevented ll-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 ll-Elemene. Conclusion: ll-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.

• 单位
  广东省人民医院; 广州中医药大学