Inhibitory effect of glutathione S-transferase A3 in the progression of cutaneous squamous cell carcinoma

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous malignancy with an incidence rate increasing each year. Glutathione S-transferase A3 (GSTA3), a member of the glutathione S-transferase family, is considered an antioxidative protease, but its role in cSCC remains unclear.

Aim: The present study was designed to explore the effect of GSTA3 on cSCC.

Patients/methods: Through previous systematic studies, we screened GSTA3 to be a key gene with lower expression in cSCC. In the present study, we selected cSCC tissues and para-carcinoma tissue specimens from 20 patients in plastic surgery department. A431 cells were treated with GSTA3 transfection. The cell proliferation, Apoptosis, colony formation, and cell migration as well as invasion were examined, respectively. And the expressions of GSTA3, TGF-β/Smad, and HIF-1α signalings were measured by Western blot and qRT-PCR.

Results: GSTA3 was downregulated in both cSCC tissues and A431 cells. Additionally, overexpression of GSTA3 induced a phenotype with a lower degree of malignancy, while GSTA3 silencing induced more malignant phenotypes, including cell proliferation, colony formation, Apoptosis, migration, and invasion. Moreover, we found that the TGF-β/SMAD2/3 and HIF-1α signalings were activated in cSCC under hypoxic conditions.

Conclusion: GSTA3 could inhibit cSCC progression through suppression of the TGF-β/Smad and HIF-1α signalings. Therefore, GSTA3 may prove to be a prospective therapeutic target for cSCC.