Tissue-specific transplantation antigen P35B functions as an oncogene and is regulated by microRNA-125a-5p in lung cancer

Abstract

Tissue-specific transplantation antigen P35B (TSTA3) expression is upregulated in esophageal squamous cell carcinoma and breast cancer, and functions as an onco- gene in breast cancer. However, the roles and underlying mechanisms of TSTA3 in lung cancer have not been fully elucidated. The current study aimed to reveal the role of TSTA3 in lung cancer and explore whether TSTA3 may be modulated by microRNA (miR)-125a-5p to activate β-catenin signaling. Immunohistochemical staining and western blotting were used to analyze TSTA3 expression in lung cancer tissues and cells. Cell functions were assessed via Cell Counting Kit-8, flow cytometry, wound-healing, Transwell and in vivo tumor formation assays. The effect of TSTA3 on the activa- tion of β-catenin signaling was determined using western blot and immunofluorescence analyses. The association between miR-125a-5p and TSTA3 was determined by western blotting and luciferase gene reporter assay. The present study revealed that, compared with normal tissues and cells, TSTA3 expres- sion was significantly increased in lung cancer tissues and cell lines, and high TSTA3 expression predicted a poor prognosis and more malignant clinical features in patients with lung cancer. TSTA3 upregulation significantly enhanced β-catenin expression and promoted its nuclear accumulation. In addition, TSTA3 expression was negatively regulated by miR-125a-5p, which was downregulated in lung cancer. Furthermore, TSTA3 overexpression markedly promoted cell proliferation, migration, invasion and tumorigenesis, and suppressed cell apoptosis. TSTA3 downregulation abolished the effects of miR-125a-5p downregulation on promoting lung cancer cell malignant transformation. Overall, the current study demon- strates that TSTA3 is regulated by miR-125a-5p and functions as an oncogene in lung cancer via promoting the activation of β-catenin signaling.