Inhibition of HMGA2 Leads to Reduced Cell Proliferation and Increased Apoptosis in Human Embryonal Carcinoma Cell Lines

Background The most prevalent solid tumors in young men are testicular germ cell tumors (TGCTs), and embryonal carcinoma is the most common subtype among non-seminomatous germ cell tumors (NSGCTs). Despite the excellent cure rates of cisplatin-based chemotherapy, resistance develops in 15%-30% of patients with metastatic cancer, which results in a poor prognosis. The overexpression of the High Mobility Group A2 (HMGA2) protein has been linked to treatment resistance and cancer aggressiveness. It is well known that this protein promotes carcinogenesis.Objective The purpose of this work was to investigate the functional role of HMGA2 in EC cell migration, survival, and proliferation, focusing on its role as a potential therapeutic target in cisplatin-resistant ECs.Materials and Methods We employed human EC cell lines EP2102 and GCT27, as well as the cisplatin-resistant (CisR) versions of these cell lines that were produced by prolonged drug treatment. siRNA transfection was used to suppress HMGA2 expression. Growth curve and colony formation tests were used to measure cell proliferation. Apoptosis was assessed by Annexin V staining followed by flow cytometry, cell cycle distribution was analyzed by flow cytometry, and cell migration was detected by Boyden Chamber Assays.Results In both parental and resistant EC cell lines, HMGA2 knockdown markedly decreased proliferation. After HMGA2 knockdown, flow cytometric analysis revealed S phase arrest. Apoptosis was significantly elevated, especially in cells that were resistant to cisplatin. In addition, all HMGA2-depleted cell lines showed decreased migration. These impacts were true for both the GCT27 and EP2102 models.Discussion The data suggest that HMGA2 is necessary to preserve the EC cells' malignant characteristics. Its silencing interferes with several cancer-related functions, including motility, survival, and cell cycle progression. These results indicate HMGA2's participation in chemoresistance mechanisms and are consistent with its role in other solid cancers.Conclusion Our results indicate a role of HMGA2 in the EC, because its inhibition reduces cell malignant characteristics, and may represent a viable therapeutic target to improve the prognosis of CisR TGCTs.