TMEM45B, up-regulated in human lung cancer, enhances tumorigenicity of lung cancer cells.

Transmembrane protein 45B (TMEM45B) is a member of TMEMs. Altered expression of TMEMs is frequently observed in a variety of human cancers, but the expression and functional roles of TMEM45B in lung cancer is not reported. In the present study, levels of mRNA expression of TMEM45B in lung cancer tissues were assessed using re-analyzing expression data of The Cancer Genome Atlas (TCGA) lung cancer cohort and real-time PCR analysis on our own cohort. Lung cancer cells, A549 and NCI-H1975, infected with TMEM45B short hairpin RNA were examined in cell proliferation, cell cycle, cell apoptosis, wound-healing, and cell invasion assays as well as mouse xenograft models. Here, we demonstrated that TMEM45B was overexpressed in lung cancer and its expression correlated with overall survival of patients. In addition, silencing of TMEM45B expression reduced cell proliferation in vitro and in vivo, induced cell cycle arrest and cell apoptosis, and blocked cell migration and invasion. Moreover, knockdown of TMEM45B significantly suppressed G1/S transition, induced cell apoptosis, and inhibited cell invasion via regulating the expression of cell cycle-related proteins (CDK2, CDC25A, and PCNA), cell apoptosis-related proteins (Bcl2, Bax, and Cleaved Caspase 3), and metastasis-related proteins (MMP-9, Twist, and Snail), respectively. Thus, TMEM45B is a potential prognostic marker and cancer-selective therapeutic target in lung cancer.