Abstract
BackgroundThe tripartite motif (TRIM) family proteins are implicated in the pathogenesis of various human malignancies. The up-regulation and oncogenic roles of TRIM52 have been reported in hepatocellular carcinoma. In the current study, we aimed to examine its expression and possible function in colorectal cancer (CRC).MethodImmunohistochemical staining or immunoblotting analysis was carried out to detect protein expression. Cell proliferation and apoptosis was evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry assay, respectively.ResultsTRIM52 expression was increased in 67.5% of CRC tissues (54/80) compared to matched normal colonic mucosa. TRIM52 expression was closely related with tumor size (p = 0.0376), tumor stage (p = 0.0227) and overall survival (p = 0.0177). Short hairpin RNAs (shRNAs) targeting TRIM52 had the potential anti-proliferative effects on CRC cell lines, SW480 and LoVo, by inducing cell apoptosis. In addition, an in vivo xenograft experiment confirmed the in vitro results. In addition, TRIM52 shRNAs decreased the phosphorylation of STAT3, but increased the protein expression of SHP2, a negative regulator of STAT3 phosphorylation. TRIM52 formed a complex with SHP2 and promoted the ubiquitination of SHP2. Furthermore, inhibition of the STAT3 signaling by AG490 in RKO cells significantly abolished the effects of TRIM52 overexpression on cell proliferation, apoptosis and STAT3 activation.ConclusionsTRIM52 might exert oncogenic role in CRC via regulating the STAT3 signaling pathway.
Highlights
The tripartite motif (TRIM) family proteins are implicated in the pathogenesis of various human malignancies
Inhibition of the Signal transducer and activator of transcription 3 (STAT3) signaling by AG490 in RKO cells significantly abolished the effects of TRIM52 overexpression on cell proliferation, apoptosis and STAT3 activation
TRIM52 protein expression is up‐regulated in human colorectal cancer (CRC) tissues To examine TRIM52 expression in CRC tissues, IHC staining was performed in archived paraffin CRC specimens and paired normal colonic mucosa specimens from 80 patients
Summary
The tripartite motif (TRIM) family proteins are implicated in the pathogenesis of various human malignancies. Continued efforts have made to improve the understanding of tumorigenesis, and numerous oncogenes and tumor suppressor genes involved in CRC tumorigenesis have been identified, the biological and molecular mechanisms of CRC are still far from being fully understood. Signal transducer and activator of transcription 3 (STAT3), a transcription factor, normally resides in the cytoplasm. When its tyrosine-705 residue is phosphorylated in response to cytokine signaling and tyrosine kinase oncoproteins, STAT3 translocates to the nucleus and controls the transcription of downstream genes that are involved in cell cycle transition and cell survival [5, 6]. The Janus family kinases (JAK) are known to mediate the activation of STAT3 [10]. AG490, a pharmacological inhibitor of JAK, and STAT3 small interfering RNA (siRNA) could suppress CRC cell growth and invasion, and induce CRC cell apoptosis [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
