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

Abstract

BackgroundSelenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium‐containing protein as a mediator. Of note, the previous studies reported that the expression of selenium‐binding protein 1 (SELENBP1) was 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.MethodsThe expression of SELENBP1 was measured by qRT‐PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK‐8, colony formation, wound‐haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay.ResultsWe further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT‐II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase‐3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress.ConclusionsOur 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.

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“…Furthermore, genes involved in cellular adhesion and inflammation, such as ICAM1, can promote neuroinflammation and disrupt blood–brain barrier integrity, thereby exacerbating AD pathological maifestation ( 28 ). Additionally, ABC transporters, including ABCB1 and ABCC2, are involved in the efflux of amyloid-beta peptides from the brain, and their dysregulation may contribute to amyloid-beta accumulation and neurotoxicity in AD ( 78 ). Finally, aldolase A (ALDOA), and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) are implicated in neuronal energy metabolism, synaptic plasticity, and neurogenesis, suggesting their involvement in AD pathophysiology ( 98 ).…”

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“…Lowered expression of SELENBP1 has been reported for many types of cancer, such as tumors of the colon, lungs, ovaries, prostate, liver, thyroid, kidneys, and breast [ 19 ]. SELENBP1 has been designated a tumor suppressor that may inhibit cell proliferation, angiogenesis, metastasis, and resistance to chemotherapy, as well as promote apoptotic cell death ( Figure 2 ) [ 19 , 55 , 56 , 57 , 58 , 59 ]. Moreover, low SELENBP1 levels in cancer tissue correlate with poor clinical prognosis for the patients [ 19 ].…”