NELFE promoted pancreatic cancer metastasis and the epithelial-to-mesenchymal transition by decreasing the stabilization of NDRG2 mRNA

Negative elongation factor E (NELFE) has been demonstrated to promote cancer progression as an RNA-binding protein (RBP). However, the expression patterns, biological role and molecular mechanism of NELFE in pancreatic cancer (PC) remain largely unknown. The expression levels of NELFE in 120 pairs of PC tissues and adjacent non-tumor clinical samples collected from patients with PC were examined via reverse transcription-quantitative (RT-q) PCR and immunohistochemistry. The mRNA expression levels of NELFE, N-Myc downstream-regulated gene 2 (NDRG2), c-Myc, survivin and cyclin D1 were detected via RT-qPCR. The protein expression levels of NELFE, NDRG2, total β-catenin, nuclear β-catenin, cytosolic β-catenin, E-cadherin, N-cadherin and Vimentin were measured by western blotting. NELFE and NDRG2 were then knocked-down by short hairpin (sh)RNA. PC cell proliferation was detected by MTT and colony formation assays. Invasion and migration were detected by transwell assays. The interaction between NELFE and NDRG2 was detected by luciferase reporter assays, mRNA decay assays and RNA immunoprecipitation. NELFE expression was increased in PC tissues compared with the paired non-cancerous tissues. NELFE expression was upregulated in PC cells when compared with normal pancreatic cells (HPDE6-C7). The present study revealed that knockdown of NELFE inhibited the proliferation, invasion and migration of PC cells. In addition, transfection of the sh-NELFE vector inhibited the epithelial-to-mesenchymal transition in PC cells by suppressing the expression and nuclear accumulation of β-catenin. Further mechanistic studies revealed that NELFE activates the Wnt/β-catenin signaling pathway by decreasing the stabilization of NDRG2 mRNA in PC. To the best of our knowledge, these results revealed the promotional function of NELFE on PC tumorigenesis and metastasis for the first time, helping to provide a promising strategy for the treatment of patients with PC.