NFE2L3 promotes malignant behavior and EMT of human hepatocellular carcinoma (HepG2) cells via Wnt/β‑catenin pathway

作者：Yonggang Ren, Yujiao Wang, Shuai Hao, Yuhan Yang, Wendong Xiong, Lu Qiu, Jia Tao, Aifa Tang · 发表于：Journal of Cancer · 年份：2020 · DOI：10.7150/jca.48100 · 被引用次数：43 · 研究领域：MicroRNA in disease regulation、Genomics, phytochemicals, and oxidative stress、RNA modifications and cancer

Objective: NFE2L3 is a member of the cap 'n' collar basic-region leucine zipper family.NFE2L3 has turned out to be associated with oxidative stress, but the relevance of NFE2L3 in hepatocellular carcinoma (HCC) has remained elusive.This study aimed to investigate the role of NFE2L3 in HCC and explore underlying mechanisms.Methods: Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the mRNA and protein expression of NFE2L3, the expression of epithelial-mesenchymal transition (EMT) markers and Wnt/β-catenin signaling pathway-related proteins.In loss-function experiments, HepG2 cells were transfected with lentiviral vector containing NFE2L3 short hairpin RNA or scramble control.Cell proliferation and migration were measured by Cell Counting Kit-8, Colony formation, EdU incorporation and Transwell assays respectively.Flow cytometry was used to analyze cell cycle and apoptosis.HepG2 cells were subcutaneously injected into nude mice and tumor size was measured once every other day.Results: The results revealed that high expression of NFE2L3 was positively associated with malignant behavior and EMT in HCC.Knockdown of NFE2L3 inhibited cell proliferation and migration, led to cell cycle G0/G1 arrest and induction of cell apoptosis, increased expression of E-cadherin and decreased expression of N-cadherin, Vimentin, MMP2, CDK2 and PCNA.In addition, tumor growth was inhibited by silencing of NFE2L3 in vivo.Expression of β-catenin and Wnt target genes ...