Down-regulated Beclin 1 expression is closely linked to lung carcinogenesis by reversing aggressive phenotypes

Abstract

\n Background\n\nBeclin1 is involved in numerous biological processes, including autophagy, stress, senescence, and death. This article aims to clarify the roles of Beclin1 expression in lung carcinogenesis and subsequent progression.\nMethods\n\nThe Beclin 1 expression was examined in lung cancer and compared it with clinicopathological parameters and survival data of the cancers using a large number of lung cancer samples. Additionally, we observed the effects of forced Beclin 1 overexpression and its silencing on the proliferation, glucose metabolism, apoptosis, autophagy, invasion, migration, lamellipodia formation, and chemoresistance of lung cancer cells and analyzed the relevant mechanisms. Finally, in vivo effects of Beclin 1 overexpression on tumor growth was determined in nude mice.\nResults\n\nBeclin 1 reversed aggressive phenotypes in SQ-5 and KJ cells with Bcl-2, HSP90, and β-catenin underexpression, LC-3B, ADFP, p-p38, and cytochrome c hyperexpression. The effect of Beclin 1 silence was opposite in H446 cells. In vivo and in vitro Beclin 1-mediated chemoresistance to cisplatin was close with the apoptotic level and NF-кB activation. Beclin 1 overexpression suppressed tumor growth of lung cancer by decreasing proliferation and inducing apoptosis and autophagy. Beclin 1 expression was down-regulated in lung cancer at both mRNA and protein levels. A higher level of Becn1 mRNA was detectable in adenocarcinoma than squamous cell carcinoma (p\u2009<\u20090.05), while versa for its protein. Becn1 mRNA expression was positively correlated with overall or post-progression survival rates of all cancer patients, even stratified by aggressive behaviors (p\u2009<\u20090.05).\nConclusions\n\nThese findings suggested that down-regulated Beclin1 expression was closely linked to the tumorigenesis and histogenesis of lung cancer. Beclin 1 might be employed as a potential target for the gene therapy of lung cancer if its chemoresistance can be ameliorated or avoided.