Let7b modulates the Wnt/β-catenin pathway in liver cancer cells via downregulated Frizzled4

Abstract

Let7 microRNA implicated in many cellular processes and participated in the progress of various tumors. Similarly, Wnt signaling pathway plays an important role in morphogenesis, differentiation, cell survival, and proliferation. However, there is little research focusing on the relevance between Let7b and Wnt/β-catenin signaling pathway, especially in liver cancer cell. To study this, human liver cancer cells HUH7 and MHCC97H were cultured, enhanced, or inhibited the expression of Let7b in two cell lines. Western blotting was used to measure the expression of Wnt signaling-related protein β-catenin and Frizzled family receptor. CD24⁺133⁺ was used as a cancer stem cell marker, and the proportion of CD24⁺133⁺ in liver cancer cell lines was observed by flow cytometry. The proliferation, invasiveness, and migration of liver cancer cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell, and wound healing assays. The research revealed that enhanced expression of Let7b decreased the expression of Frizzled4, while inhibited Let7b expression increased Frizzled4 expression. Enhanced Let7b expression reduced the proportion of cancer stem cell in liver cancer cell; meanwhile, Let7b inhibition increased the proportion of cancer stem cell. Upregulated Let7b expression repressed the proliferation, invasion, and migration of liver cancer cell. This study showed that Let7b modulates the proliferation, invasiveness, and migration of liver cancer cell and reduces the proportion of cancer stem cells in liver cancer cell by inhibiting Wnt/β-catenin signaling pathway via downregulated Frizzled4.

Keywords: Frizzled4; Let7b; Liver cancer cell; Wnt/β-catenin pathway.