AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway

Abstract

Abstract. Axis inhibition protein 1 (AXIN1) is characterized as a tumor suppressor in numerous types of cancer. However, the functional role of AXIN1 in the testicular germ cell tumors (TGCTs) remains unclear. The human embryonal carcinoma-derived cell line NTera2 was transfected with a recombinant AXIN1 expression vector (pcDNA3.1-AXIN1) and/or a small interfering RNA (siRNA) directed against AXIN1 (siAXIN). Following transfection, the mRNA and protein levels of AXIN1 were determined via reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. In addition, cell viability, apoptosis and the expression of apoptosis-associated proteins [apoptosis regulator Bax (Bax) and B-cell lymphoma (Bcl)-2] and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway proteins [phosphorylated (p)-mTOR, mTOR, p-AKT, AKT, P-70S ribosomal protein S6 (S6) and S6] were assessed. AXIN1 mRNA and protein levels were increased following transfection with pcDNA3.1-AXIN1 and decreased following transfection with siAXIN1 compared with their respective control groups. After overexpression of AXIN1, NTera2 cell viability and expression of Bcl-2, p-mTOR p-AKT and p-S6 protein was decreased, while apoptosis and Bax protein levels were increased, compared with the control group. However, there was no significant difference in AXIN1 mRNA expression, apoptosis or Bax/Bcl-2 protein expression when NTera2 cells were simultaneously transfected with pcDNA3.1-AXIN1+siAXIN1. In conclusion, the results of the present study indicate that overexpression of AXIN1 protects against TGCTs via inhibiting the PI3K/AKT/mTOR signaling pathway, suggesting that AXIN1 may be a potential target for gene therapy in TGCTs.

The Clinicopathological Features and Genetic Mutations in Gastric Cancer Patients According to EMAST and MSI Status

“…It was reported that upregulation of PI3K/AKT pathway was observed in tumors with mismatch repair deficiency, including MSH2-mutant tumors [16]. In addition, overexpression of AXIN1 protected against tumors via inhibiting the PI3K/AKT pathway [17]. We speculate that mutations of MSH2 and AXIN1 may be involved in the PI3K/AKT pathway and play an important role in both EMAST+ and MSI-H tumors originating from gastrointestinal tract cancer.…”

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

“…Compared to the noted KRAS and NRAS mutations in TGCTs [286], the overall genetic alterations frequency of PIK3CA (3%), PIK3R1 (1.3%), AKT1 (0.7%) and PTEN (0.7%) are much less, even though mutations in PIK3CA and AKT1 are observed exclusively in cisplatin-resistant TGCTs [287]. AXIN1, TDRG1 and LncRNA H19 regulate cell viability, apoptosis or cisplatin resistance via the PI3K/ AKT/mTOR signaling pathway [288][289][290]. Unfortunately, PI3K/AKT inhibitors have not yet applied in clinical trials of TGCT patients up to now.…”

A Random Forest-Based Genome-Wide Scan Reveals Fertility-Related Candidate Genes and Potential Inter-Chromosomal Epistatic Regions Associated With Age at First Calving in Nellore Cattle

“…Furthermore, some genes identified in the BTA 25 may have a deleterious role on male andrological parameters, such as the Calpain-15 ( CAPN15 ), which has a causal variant affecting cryptorchidism susceptibility in rats ( Barthold et al, 2016 ). It is biologically plausible that several genes have pleiotropic effects on both male and female fertility traits, for instance, the AXIN1 is requested for successful embryo development ( Xie et al, 2011 ) and has been shown to act as a suppressor of testicular germ cell tumors ( Xu et al, 2017 ). Similarly, the APOBEC1 controls testicular germ cell tumor susceptibility and embryonic viability through transgenerational epigenetic inheritance ( Nelson et al, 2012 ).…”