Poly(rC) binding protein 2 (PCBP2) promotes the viability of human gastric cancer cells by regulating CDK2

• Published in: FEBS open bio Vol. 8; no. 5; pp. 764 - 773
• Main Authors: Chen, Changyu, Lei, Jun, Zheng, Qiang, Tan, Sheng, Ding, Keshuo, Yu, Changjun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2018; John Wiley and Sons Inc; Wiley
• Subjects: Binding sites; Biotin; Cancer therapies; cancer therapy; CDK2; Cell cycle; cyclin-dependent kinase; Cyclin-dependent kinase 2; Gastric cancer; humans; Immunoprecipitation; Kinases; Medical prognosis; mRNA; oncogenes; PCBP2; Polyclonal antibodies; precipitin tests; Proteins; ribonucleoproteins; RNA-binding protein; RNA-binding proteins; stomach neoplasms; viability; United States > US; China; gastric cancer; CDK2; PCBP2; viability
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.12408

Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly(rC) binding protein 2 (PCBP2) is an RNA‐binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues. A high level of PCBP2 was correlated with worse postoperative relapse‐free survival and overall survival rates of gastric cancer patients. Small hairpin RNA‐mediated depletion of PCBP2 dramatically decreased the viability of gastric cancer cells. Cyclin‐dependent kinase 2 (CDK2) was positively regulated by PCBP2 via a direct 3′ UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. CDK2 mediated the promoting role of PCBP2. These results suggest that PCBP2 acts as an oncogene in human gastric cancer cells and that functionally depleting PCBP2 could be considered as a potential target for gastric cancer therapy. Poly(rC) binding protein 2 (PCBP2) is over‐expressed in human gastric cancer. A high level of PCBP2 was correlated with worse post‐operative relapse‐free survival and overall survival rates of gastric cancer patients. PCBP2 knockdown dramatically decreased the proliferation of gastric cancer cells. PCBP2 increased the stability of cyclin‐dependent kinase 2 (CDK2) mRNA transcripts. CDK2 might mediate the tumor‐promoting role of PCBP2 in gastric cancer cells.