POU2F2-oriented network promotes human gastric cancer metastasis

Abstract

Background and aimsAberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain.DesignThe role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-β) and GC metastasis was further explored via in vitro and in vivo approaches.ResultsIncreased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network.ConclusionsThis study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment.

Comprehensive epigenetic analyses reveal master regulators driving lung metastasis of breast cancer

“…Especially, specific promoters in LM2‐4175 were significantly enriched in as many as 19 factors, such as TFAP2C, POU2F2 and LMO4, and most of these factors were up‐regulated in LM2‐4175. Both POU2F2 and TFAP2C are proved critical regulators of tumorigenicity, EMT and metastasis, suggesting the reliability of our epigenetic analysis for identifying master regulators. However, the function of LMO4 in lung metastasis was rarely reported, and still needed further evaluation.…”

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

“…[6][7][8][9][10] Recent studies indicate that the inactivation of this pathway is associated with the progression of several cancer types, [11][12][13] including pancreatic cancer, 14 breast cancer, 15 as well as lung tumours. 19,20 Ubiquitin-specific protease 33 (USP33), a member of ubiquitinspecific protease family, was initially identified as a substrate molecule which binds to VHL E3 ligase. A number of studies supported the notion that Slit-Robo signalling plays an important role in anti-tumour processes.…”

Upregulation of ZBTB7A exhibits a tumor suppressive role in gastric cancer cells

“…Statistical analysis identified that percentage of apoptotic cells in the OE group was significantly increased compared with the Upregulation of ZBTB7A suppresses cell migration. The migratory and invasive ability is another key characteristic of GC cells, which facilitates metastasis to other organs and results in a poor prognosis in patients (29,30). In the present study, the migration assay test was used to investigate the potential impact of upregulation of ZBTB7A on GC cell migration (Fig.…”