Effects of the long and short isoforms of TIPE3 on the growth and metastasis of gastric cancer.

Tumor necrosis factor alpha-induced protein 8-like 3 (TIPE3, also known as TNFAIP8L3) plays a vital role in tumorigenesis and development. However, it is unclear whether the two transcript variants of TIPE3 (long TIPE3 and short TIPE3) have an effect on the proliferation and metastasis of gastric cancer (GC). In this study, we demonstrated that the expression of TIPE3 decreased in GC, but patient prognosis worsened as TIPE3 expression increased. Then, overexpression models were constructed to study the role of long TIPE3 and short TIPE3. Upregulation of long TIPE3 and short TIPE3 promoted GC cell proliferation and metastasis both in vitro and in vivo, and the effect of short TIPE3 was more obvious. Further studies demonstrated that long TIPE3 and short TIPE3 promoted proliferation and metastasis of GC cells vis PI3K/Akt pathway. In conclusion, the two TIPE3 isoforms play an important role in the tumorigenesis of GC and depend on the activation of the PI3K/Akt pathway.