Abstract
BackgroundAccumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC.MethodsNELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections.ResultsNELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other.ConclusionOur findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.
Highlights
Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis
Casein kinase 2 beta (CSNK2B) was identified as a downstream effector of NELFE
The result showed that the mRNA level of NELFE was remarkably elevated in gastric cancer (GC) tissues (P < 0.0001, Fig. 1d), among which 18 cases (64.29%) exhibited an increase of more than 1.5-fold change (Fig. 1c)
Summary
Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. Dynamic regulation of transcription elongation shortly after initiation by RNA polymerase II (RNAPII) plays key roles in the implementation of gene expression widespread in metazoans [1, 2] This step is modulated by positive and negative transcription elongation factors which are known as P-TEF and N-TEF, respectively [3, 4]. Oncogenic activation of NELFE promotes hepatocellular carcinoma (HCC) cell proliferation and predicts the strong metastatic potential of HCC cells [12], whereas knockdown of NELFE results in enhanced cell colony growth of breast cancer cells when treated with estrogen-like reagents [13] While these findings implicate a critical role of NELFE in cancers, its specific functions and underlying molecular mechanisms are not fully understood
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