PCDHGA9 acts as a tumor suppressor to induce tumor cell apoptosis and autophagy and inhibit the EMT process in human gastric cancer

Abstract

The results of a cDNA array revealed that protocadherin gamma subfamily A, 9 (PCDHGA9) was significantly decreased in SGC-7901 gastric cancer (GC) cells compared with GES-1 normal gastric cells and was strongly associated with the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. As a member of the cadherin family, PCDHGA9 functions in both cell–cell adhesion and nuclear signaling. However, its role in tumorigenicity or metastasis has not been reported. In the present study, we found that PCDHGA9 was decreased in GC tissues compared with corresponding normal mucosae and its expression was correlated with the GC TNM stage, the UICC stage, differentiation, relapse, and metastasis (p < 0.01). Multivariate Cox analysis revealed that PCDHGA9 was an independent prognostic indicator for overall survival (OS) and disease-free survival (DFS) (p < 0.01). The effects of PCDHGA9 on GC tumor growth and metastasis were examined both in vivo and in vitro. PCDHGA9 knockdown promoted GC cell proliferation, migration, and invasion, whereas PCDHGA9 overexpression inhibited GC tumor growth and metastasis but induced apoptosis, autophagy, and G1 cell cycle arrest. Furthermore, PCDHGA9 suppressed epithelial–mesenchymal transition (EMT) induced by TGF-β, decreased the phosphorylation of Smad2/3, and inhibited the nuclear translocation of pSmad2/3. Our results suggest that PCDHGA9 might interact with β-catenin to prevent β-catenin from dissociating in the cytoplasm and translocating to the nucleus. Moreover, PCDHGA9 overexpression restrained cell proliferation and reduced the nuclear β-catenin, an indicator of Wnt/β-catenin pathway activation, suggesting that PCDHGA9 negatively regulates Wnt signaling. Together, these data indicate that PCDHGA9 acts as a tumor suppressor with anti-proliferative activity and anti-invasive ability, and the reduction of PCDHGA9 could serve as an independent prognostic biomarker in GC.

LINC02163 regulates growth and epithelial-to-mesenchymal transition phenotype via miR-593-3p/FOXK1 axis in gastric cancer cells

“…We also revealed that LINC02163 down-regulation inhibited GC cell invasion in vitro and decreased lung metastasis in vivo. The EMT plays vial role in promoting cancer cell invasion [25]. We thus asked whether LINC02163 was involved in EMT phenotype.…”

Peer Review #3 of "Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement (v0.2)"

“…PCDHGA, PCDHGB, PCDHGC) may contribute to cell migration and invasion. Previous studies have confirmed that PCDH genes were involved in tumorigenesis and metastasis of gastric cancer, follicular lymphoma and non-small cell lung cancer (Mukai et al, 2017;Zhang et al, 2016;Zhou et al, 2017), although other studies have found that PCDH genes were implicated in tumor suppression (Chen et al, 2017;Weng et al, 2018). However, the role of PCDH genes in MLL-R ALL is currently unclear.…”

LINC01287 regulates tumorigenesis and invasion via miR‐298/MYB in hepatocellular carcinoma

“…We also revealed that LINC01287 down‐regulation inhibited GC cell invasion in vitro and decreased lung metastasis in vivo. The EMT plays vital role in promoting cancer cell invasion . We thus asked whether LINC01287 was involved in EMT phenotype.…”

“…The EMT plays vital role in promoting cancer cell invasion. 19 We thus asked whether LINC01287 was involved in EMT phenotype. It was revealed that LINC01287 down-regulation increased epithelial marker E-cadherin while decreased mesenchymal markers N-cadherin and vimentin expression.…”