title: Bcl-2 down-regulation by small interfering RNA induces Beclin1-dependent autophagy in human SGC-7901 cells.
abstract: While Bcl-2 protein is involved in the regulation of apoptosis, recent research showed that Beclin1, described as the essential autophagy effector and haploinsufficient tumor suppressor, was originally isolated as a Bcl-2 interacting protein. Beclin1 interacts with Bcl-2 through a BH3 domain; nevertheless, the function of the anti-apoptotic gene, Bcl-2, in autophagy is not well understood. We explored the role of Bcl-2 in autophagy in human SGC-7901 cells in which Bcl-2 is overexpressed. Knockdown of Bcl-2 by small interfering RNA in human SGC-7901 cells downregulated Bcl-2 protein levels ∼82% and induced autophagy. Beclin1 protein, the first identified autophagy gene product, was induced by as much as 58%. Transmission electron microscopy and DNA fragmentation assay showed that autophagy was enhanced, but not apoptosis, in Bcl-2 siRNA treated cells. The results provide evidence that knockout the anti-apoptotic gene Bcl-2 induces autophagy in SGC-7901 cells and Bcl-2 specific siRNA may be used as a potential therapeutic strategy in gastric cancer cells that overexpress Bcl-2.
authors.affiliation: The Fourth Hospital of Hebei Medical University, Hebei Province China-Japan Friendship Center for Cancer Detection, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Du
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Ji
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering
keywords: Bcl-2 siRNA; Beclin1; apoptosis; autophagy; post-transcriptional gene silencing (PTGs)