Abstract
BackgroundColorectal cancer (CRC) is one of the most lethal malignancies. Tripartite Motif Containing 14 (TRIM14) is a member of TRIM family proteins, which are involved in the pathogenesis of various cancers. This study aimed to investigate TRIM14 expression in CRC tissues, and its effects on the migration and invasion of CRC cell lines.MethodsTRIM14 mRNA expression was detected by real-time PCR analysis. Cell migration and invasion were measured by Transwell assays. Protein expression was assessed by western blot analysis.ResultsThe expression of TRIM14 was significantly higher in CRC tissues than in matched non-cancerous tissues. TRIM14 knockdown by specific short hairpin RNA (shRNA) attenuated CRC cell migration and invasion, whereas TRIM14 overexpression caused reverse effect. Moreover, TRIM14 positively regulated the protein levels of sphingosine kinase 1 (SPHK1) and phosphorylated STAT3 (p-STAT3), as well as the mRNA and protein expression of matrix metalloproteinase 2, MMP9 and vascular endothelial growth factor, which are transcriptional targets of the STAT3 signaling pathway. Importantly, the blockage of the SPHK1/STAT3 signaling pathway by SKI-II or AG490 could reverse the TRIM14-promoted CRC cell migration and invasion.ConclusionsOur results reveal a critical role for TRIM14 in promoting migration and invasion of CRC cells, and suggest TRIM14 may serve as a potential molecular target to prevent CRC metastasis.
Highlights
Colorectal cancer (CRC) is one of the most lethal malignancies
Up‐regulation of Tripartite Motif Containing 14 (TRIM14) mRNA expression in CRC tissues We tested the mRNA expression of TRIM14 in CRC tissues and matched non-cancerous tissues by real-time PCR analysis
TRIM14 promoted CRC cell migration and invasion We explored whether TRIM14 expression affected CRC cell migration and invasion
Summary
Colorectal cancer (CRC) is one of the most lethal malignancies. Tripartite Motif Containing 14 (TRIM14) is a member of TRIM family proteins, which are involved in the pathogenesis of various cancers. The main reason of high mortality rate in CRC patients is the extreme difficulty in treating distant metastases [1]. The feature characteristics of aggressive metastatic cancers include high ability of migration, consequent invasion and adhesion in the distant organs [2]. Members of the tripartite motif (TRIM) family, called the RING B-box-coiled-coil (RBCC) family, are involved in the pathogenesis of various cancers by acting as STAT3 belongs to the signal transducer and activator of transcription (STAT) family, which is activated by the upstream stimuli, such as cytokines, growth factors and non-receptor tyrosine kinases.
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