Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small-cell lung cancer.

Selenium is an essential trace element in the human body. The significant action of selenium is based on the selenium-containing protein as a mediator. Of note, previous studies reported that the expression of selenium-binding protein 1 (SELENBP1) has obviously decreased in many human cancer tissues including non-small-cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. Here, we further identified that the expression of SELENBP1 was dramatically decreased in NSCLC tissues in the TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues as well as four NSCLC cell lines compared with normal lung cells. Then a series of in vitro experiments uncovered that overexpression of SELENBP1 markedly inhibited the proliferation, migration, and invasion of NSCLC cells and induced cell apoptosis. Moreover, overexpression of SELENBP1 also observably inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1-inducing apoptosis of NSCLC cells was associated with the activation of the caspase-3-dependent signaling pathway under nonhigh levels of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis was related to its combining with GPX1 and colocalizing in the nucleus under high levels of oxidative stress. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT-II) cells for the first time. Collectively, our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.