TRIM14 promotes colorectal cancer cell migration and invasion through the SPHK1/STAT3 pathway

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.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0701-1) contains supplementary material, which is available to authorized users.

<p>TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer</p>

“…Recently, we have reported that TRIM14 mRNA levels were elevated in CRC tissues. 22 In the current study, IHC analysis confirmed the above findings at the translational level. Further, our data suggested that elevated expression of TRIM14 in CRC tissues was closely related to the aggressive clinicopathological characteristics and poor patient prognosis (Figure 1).…”

“…The results of our recent study 22 indicated that TRIM14 was upregulated in CRC and promoted the migration and invasion of CRC cells. In the current study, we further probed the correlation between TRIM14 expression and CRC patient prognosis, and went on to investigate the functions of TRIM14 on CRC cell proliferation and apoptosis.…”

“…Lentiviral plasmids expressing control short hairpin RNA (shRNA) (shNC) or TRIM14 shRNAs (shTRIM14-1, 2, 3), and TRIM14 or PTEN complementary DNAs (cDNAs) were constructed, and lentiviruses were produced as previously described. 22…”

“…Given that TRIM14 expression was significantly correlated with tumor size, we then explored the potential roles of TRIM14 in CRC cell proliferation by knocking down TRIM14 in HT-29 and SW620 cells using TRIM14 shRNA, or by overexpressing TRIM14 in LoVo cells by lentiviral infection as previously described. 22 TRIM14 protein expression was assessed by Western blotting at 48 hrs post-lentiviral infection. As shown in Figure 2A, TRIM14 protein levels were nearly abolished in cells with shTRIM14-1.…”

A Novel Gene Signature-Based Model Predicts Biochemical Recurrence-Free Survival in Prostate Cancer Patients after Radical Prostatectomy

“…SSTR1 was widely related to the progression of various cancers [28][29][30], and also functions as a prognostic marker in prostate cancer [31,32]. TRIM14 has been reported to promote invasion in glioblastoma [33] and colorectal cancer [34]. SRD5A2, one protective biomarker in our study, inhibits the invasion of prostate cancer cells via regulating the ERK/MAPK pathway [35], and polymorphism in SRD5A2 contributes to resistance to androgen-deprivation therapy [36].…”