Effects of the long and short isoforms of TIPE3 on the growth and metastasis of gastric cancer
BIOMEDICINE & PHARMACOTHERAPY
Authors: Gao, Jie-Fang; Zhang, Hong; Lv, Jian; Fan, Yue-Ying; Feng, Dou; Song, Ling
Abstract
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.
A genome-wide association study of growth and fatness traits in two pig populations with different genetic backgrounds
JOURNAL OF ANIMAL SCIENCE
Authors: Jiang, Y.; Tang, S.; Wang, C.; Wang, Y.; Qin, Y.; Wang, Y.; Zhang, J.; Song, H.; Mi, S.; Yu, F.; Xiao, W.; Zhang, Q.; Ding, X.
Abstract
Improvement in growth and fatness traits are the main objectives in pig all breeding programs. Tenth rib backfat thickness (10RIBBFT) and days to 100 kg (D100), which are good predictors of carcass lean content and growth rate, respectively, are economically important traits and also main breeding target traits in pigs. To investigate the genetic mechanisms of 10RIBBFT and D100 of pigs, we sampled 1,137 and 888 pigs from 2 Yorkshire populations of American and British origin, respectively, and conducted genome-wide association study (GWAS) through combined analysis and meta-analysis, to identify SNPs associated with 10RIBBFT and D100. A total of 11 and 7 significant SNPs were identified by combined analysis for 10RIBBFT and D100, respectively. And in meta-analysis, 8 and 7 significant SNPs were identified for 10RIBBFT and D100, respectively. Among them, 6 and 5 common significant SNPs in two analysis results were, respectively, identified associated with 10RIBBFT and D100, and correspondingly explained 2.09% and 0.52% of the additive genetic variance of 10RIBBFT and D100. Further bioinformatics analysis revealed 10 genes harboring or close to these common significant SNPs, 5 for 10RIBBFT and 5 for D100. In particular, Gene Ontology analysis highlighted 6 genes, PCK1, ANGPTL3, EEF1A2, TNFAIP8L3, PITX2, and PLA2G12, as promising candidate genes relevant with backfat thickness and growth. PCK1, ANGPTL3, EEF1A2, and TNFAIP8L3 could influence backfat thickness through phospholipid transport, regulation of lipid metabolic process through the glycerophospholipid biosynthesis and metabolism pathway, the metabolism of lipids and lipoproteins pathway. PITX2 has a crucial role in skeletal muscle tissue development and animal organ morphogenesis, and PLA2G12A plays a role in the lipid catabolic and phospholipid catabolic processes, which both are involved in the body weight pathway. All these candidate genes could directly or indirectly influence fat production and growth in Yorkshire pigs. Our findings provide novel insights into the genetic basis of growth and fatness traits in pigs. The candidate genes for D100 and 10RIBBFT are worthy of further investigation.