TRIM52 promotes colorectal cancer cell proliferation through the STAT3 signaling

• Main Authors: Shengli Pan, Yingying Deng, Jun Fu, Yuhao Zhang, Zhijin Zhang, Xiaokun Ru, Xianju Qin
• Format: Article
• Language: English
• Published: BMC 2019-03-01
• Series: Cancer Cell International
• Subjects: TRIM52; Proliferation; Prognosis; STAT3
• Online Access: http://link.springer.com/article/10.1186/s12935-019-0775-4

Abstract Background The 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). Method Immunohistochemical 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. Results TRIM52 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. Conclusions TRIM52 might exert oncogenic role in CRC via regulating the STAT3 signaling pathway.