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

Abstract

Ethnopharmacological relevanceHepatocellular 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 researchLncRNA 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 methodsMTT, 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. Resultsβ-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. Conclusionβ-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.