TRIB2 Inhibits Senescence Of Colorectal Cancer Cells Via AP4/p21 Signal Axis

TRIB2 is a member of the TRBs family that has a kinase-like structure but not an ATP-binding site,therefore lacking kinase activity.It acts as a scaffold protein or adaptor protein and plays an important role in a variety of cellular processes.Cellular senescence is defined as a state of irreversible cell cycle arrest,which is closely related to tumor development and treatment.The role of TRIB2 in tumor cell senescence is currently unclear.In this study we found that TRIB2 promotes cell proliferation and inhibits senescence through AP4/p21 signaling pathway.Specifically,the expression of TRIB2 in colorectal tumor tissues was significantly higher than that in adjacent normal tissues,and its expression was negatively correlated with clinical prognosis.Knockdown of TRIB2 inhibited cell proliferation and promoted cell senescence,while overexpression of TRIB2 promoted cell proliferation and inhibited cell senescence.TRIB2 can inhibit the expression of p21 in a p53-independent manner.In terms of mechanism,TRIB2 can directly bind to AP4,enhance the ability of AP4 to bind to the p21 promoter region,inhibit the transcriptional activity of p21,and then inhibit p21 expression.The results in this study reveal that TRIB2 is an important molecule regulating cell senescence and provides a new target for the treatment of tumors by inducing cell senescence.