SerpinE2 promotes multiple cell proliferation and drug resistance in osteosarcoma

Abstract

SerpinE2 is a member of the Serpins family, which could inhibit serine protease and promote tumor progression, particularly in tumor metastasis. However, at present, its role in the progression of osteosarcoma has not been determined. The present study analyzed the expression profiles of SerpinE2 in cancer tissues, including tissues from osteosarcoma of different stages. Higher expression of SerpinE2 was shown in osteosarcoma tissues, particularly in tissue from patients with metastasis and a tumor-node-metastasis stage II‑III. Following chemotherapy, the SerpinE2 expression levels were shown to be higher than those at diagnosis. Cell proliferation and colony formation were increased after transfection with SerpinE2 over‑expression vector. Additionally, drug resistance to bortezomib and doxorubicin treatment following SerpinE2 transfection was analyzed. MG‑63 and SAOS‑2 cells showed less sensitivity following transfection with SerpinE2. The cell cycle‑related genes, cyclin‑dependent kinase (CDK)4 and cyclin D1 were positively correlated with SerpinE2 expression in patient‑derived tissue and in osteosarcoma cells. Finally, the high expression of SerpinE2 contributes to poor survival rates in patients with osteosarcoma. In conclusion, high expression of SerpinE2 in osteosarcoma stimulates cell proliferation, promotes drug‑resistance, and results in poor survival by regulating CDK4 and cyclin D1. Thus, SerpinE2 could be a potential target for treatment of patients with osteosarcoma.

High Expression Level of Serpin Peptidase Inhibitor Clade E Member 2 is Associated with Poor Prognosis in Lung Adenocarcinoma

“…Using the GEPIA database, we found that high SERPINE2 mRNA expression was also related to poor prognosis. The overall results for survival showed the same trend as that observed in previous reports on different cancers, including breast cancers [3], gastric cancers [9] and osteosarcomas [20]. Regarding the molecular mechanism, in vitro analysis revealed that SERPINE2 plays a possible antiapoptotic role, leading to the development of malignant features in cancer cells with high SERPINE2 expression.…”

“…SERPINE2 was proven to be a member of the SERPINE family, which has serine protease activity [1,7]. SERPINE2 is overexpressed in a variety of cancers, including breast cancer [3], pancreatic cancer [8], gastric cancer [9], osteosarcoma [10] and colorectal cancer [11], and its expression is correlated with the degree of cancer malignancy. A previous study demonstrated that SERPINE2 is upregulated by oncogenic activation of RAS, BRAF and MEK1 and contributes to pro-neoplastic actions of ERK signaling in intestinal epithelial cells [11].…”

Expression pattern of human SERPINE2 in a variety of human tumors

“…In osteosarcoma, SERPINE2 expression is higher in tissue from patients with metastasis and a tumor-node-metastasis stage II-III, and increases after chemotherapy. In vitro experiments show that SERPINE2 can stimulate cell proliferation and promote drug-resistance in osteosarcoma (19). Thus SERPINE2 appears pro-neoplastic in such scenarios (15).…”

“…The potential values of SERPINE2 in the prognosis of several cancers and its co-expression with target proteases in the tumor microenvironment announce its role in tumor progression. SERPINE2 is overexpressed in many cancers including breast cancer (6), pancreatic cancer, gastric cancer, colorectal cancer (14)(15)(16), thyroid cancer (17), oral carcinoma (18) and osteosarcoma (19), and contributes to tumor invasion and metastasis. It has been identified that up-regulation of SERPINE2 is related to oncogenic activation of RAS, BRAF and MEK, which leads to the pro-neoplastic actions of extracellular signal-regulated kinase (ERK) signaling in intestinal epithelial cells (15).…”

“…It has been identified that up-regulation of SERPINE2 is related to oncogenic activation of RAS, BRAF and MEK, which leads to the pro-neoplastic actions of extracellular signal-regulated kinase (ERK) signaling in intestinal epithelial cells (15). SERPINE2 could also promote drug resistance in osteosarcoma (19) and lymph node metastasis in testicular germ cell tumors (20). Fayard has described a novel pathway where SERPINE2, by binding to lipoprotein receptor-related protein (LRP)-1, stimulates ERK signaling and matrix metalloproteinase (MMP)-9 expressions and promotes the metastatic spread of mammary tumors (6).…”