Bioimpacts. 2019;9(3):145-159.
doi: 10.15171/bi.2019.19
  Abstract View: 90
  PDF Download: 2

Original Research

Functional expression and impacts of testis-specific gene antigen 10 in breast cancer: a combined in vitro and in silico approach

Abstract

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 expression HIF-1α 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 protein-protein 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 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: TSGA10 functional expression alters under the hyper-/hypo-glycemia and hypoxia, which indicates its importance as a candidate bio-target for cancer therapy.

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Submitted: 25 Sep 2018
Revised: 20 Feb 2019
Accepted: 02 Mar 2019
First published online: 08 Mar 2019
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