SELENBP1 Inhibits Cell Proliferation and Migration in Colorectal Cancers by Suppressing EMT

Abstract

Listen

Translate article

Background: Selenium binding protein 1 (SELENBP1) is frequently dysregulated in various malignancies including colorectal cancer (CRC). Methods: Expression of SELENBP1 in colorectal normal tissues (NTs) and CRCs was determined using bioinformatics data and clinical samples. Correlation between SELENBP1 expression and patient survival was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate survival analyses were conducted with a Cox proportional hazards regression model. The impact of SELENBP1 on cell proliferation, migration and invasion, and in vivo tumorigenesis were investigated by Cell Counting Kit-8 (CCK8) assay and EdU assay, Transwell migration and invasion assays, and a subcutaneous xenograft model. The underlying mechanism was characterized for the suppressive roles of SELENBP1 in CRC carcinogenesis and progression. Findings: The expression of SELENBP1 was significantly and consistently decreased in CRCs than that in NTs, while significantly and frequently decreased in metastatic than primary CRCs. High expression of SELENBP1 was an independent predictor of favorable prognoses in CRC patients. Overexpression of SELENBP1 suppressed, while silencing of SELENBP1 promoted cell proliferation, migration and invasion, and in vivo tumorigenesis of CRC. Mechanically, SELENBP1 may suppress CRC carcinogenesis and progression by inhibiting the epithelial-mesenchymal transition (EMT). Interpretation: our results demonstrate that SELENBP1 could be a promising tumor suppressor which should be further investigated. Funding: This work was supported by Shanghai Fifth People’s Hospital (grant numbers 2016WYRC01 and 2017WYRCSG01); the Medical System of Shanghai Minhang District (grant number 2017MWDXK01); the Shanghai Minhang District Health and Family Planning Commission (grant number 2016MW03); and the Shanghai Minhang District Science and Technology Commission (grant numbers 2017MHZ02, 2019MHZ054, and 2020MHZ080). Declaration of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by the Institutional Ethics Committee at Shanghai Fifth People’s Hospital and adhered to the principles listed in the Declaration of Helsinki.