| Introduction: Testis-specific gene antigen
10 (TSGA10) is a less-known gene, which
is involved in the vague biological paths
of different cancers. Here, we investigated
the TSGA10 expression using different
concentrations of glucose under hypoxia and
also its interaction with the hypoxia-inducible
factor 1 (HIF-1).
Methods: The breast cancer MDA-MB-231
and MCF-7 cells were cultured with different
concentrations of glucose (5.5, 11.0 and 25.0
mM) under normoxia/hypoxia for 24, 48, and 72 hours and examined for the HIF-1α expression
and cell migration by Western blotting and scratch assays. The qPCR was employed to analyze
the expression of TSGA10. Three-dimensional (3D) structure and the energy minimization of
the interacting domain of TSGA10 were performed by MODELLER v9.17 and Swiss-PDB viewer
v4.1.0/UCSF Chimera v1.11. Hex 8.0.0, STRING v10.5, Cytoscape v3.6.0, and CellDesigner v4.4.0
were respectively used for the molecular docking between TSGA10 and HIF-1α, the proteinprotein interaction (PPI) network of TSGA10 and HIF-1α, the main enriched functional and
molecular processes, and the signaling pathway of TSGA10 and HIF-1α.
Results: The increased expression of TSGA10 was found to be significantly associated with the
reduced metastasis in the MDA-MB-231 cells, while an inverse relationship was seen between the
TSGA10 mRNA level and cellular migration but not in the MCF-7 cells. The C-terminal domain
of TSGA10 interacted with HIF-1α with high affinity, resulting in PPI network with 10 key nodes
(HIF-1α, VEGFA, HSP90AA1, AKT1, ARNT, TP53, TSGA10, VHL, JUN, and EGFR).
Conclusions: Collectively, TSGA10 functional expression alters under the hyper-/hypo-glycemia
and hypoxia, which indicates its importance as a candidate bio-target for the cancer therapy |