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

Abstract

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 ( PCBP 2) 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 PCBP 2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues. A high level of PCBP 2 was correlated with worse postoperative relapse‐free survival and overall survival rates of gastric cancer patients. Small hairpin RNA ‐mediated depletion of PCBP 2 dramatically decreased the viability of gastric cancer cells. Cyclin‐dependent kinase 2 ( CDK 2) was positively regulated by PCBP 2 via a direct 3′ UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. CDK 2 mediated the promoting role of PCBP 2. These results suggest that PCBP 2 acts as an oncogene in human gastric cancer cells and that functionally depleting PCBP 2 could be considered as a potential target for gastric cancer therapy.

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

“…The ectopic expression of p42 and/or p45 hnRNP D isoforms in hnRNP D-deleted mouse embryonic fibroblasts demonstrated that such isoforms are able to bind TERT promoter and to strongly transactivate TERT expression, thus reducing cell senescence (Pont et al, 2012). The hnRNP E1 plays a major role in the production of integrin β1A isoform, whose expression has been found to correlate with lymph node and hepatic metastasis of pancreatic cancer, while the upregulation of hnRNP E2 was shown to promote the expression of CDK2 causing increased proliferation of gastric cancer cells (Jiang et al, 2017;Chen C. et al, 2018).…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…Many other RBPs also exhibit changed expression in GC tissues. The hnRNP‐A1, ‐A2/B1, ‐C, ‐F, ‐K, polypyrimidine tract‐binding protein (PTBP)‐1, ‐3, poly r(C) binding protein 2, IMP‐3, Musashi‐1, and non‐POU domain containing octamer binding protein (NONO) were upregulated (C. Chen et al, ; Huang et al, ; Jing et al, ; P. T. Lee et al, ; D. Li et al, ; Park et al, ; Shou et al, ; Sugiyama et al, ; S. H. Xu et al, ; R. Yang et al, ; Zhou et al, ), while RNA‐binding motif (RBM)‐4, ‐5, RBM single‐stranded interacting protein 3 (RBMS3), and PCBP1 were inhibited (Ji et al, ; Kobayashi et al, ; Y. Wu et al, ; Yong et al, ; T. Zhang et al, ). These aberrant expression patterns were thought to associate with pathologic feature and survival of GC patients, but further investigations are needed to reveal their functions and direct targets during cancer development.…”

H3K27ac-induced lncRNA PAXIP1-AS1 exhibits oncogenic property in ovarian cancer by targeting miR-6744-5p/PCBP2 axis

“…As reported, PCBP2 was involved in cell proliferation and migration in bladder cancer [31]. PCBP2 enhanced cell viability through regulating CDK2 in gastric cancer [32]. PCBP2 was overexpressed in glioblastoma and associated with unfavorable prognosis [33].…”