We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Silencing of JMJD2B induces cell apoptosis via mitochondria-mediated and death receptor-mediated pathway activation in colorectal cancer.
- Authors
Sun, Bei Bei; Fu, Lin Na; Wang, Yun Qian; Gao, Qin Yan; Xu, Jie; Cao, Zhi Jun; Chen, Ying Xuan; Fang, Jing Yuan
- Abstract
Objective To investigate the molecular mechanism of colorectal cancer ( CRC) cell apoptosis induced by the Jumonji domain containing 2B ( JMJD2B) silencing. Methods Both HCT116 and LoVo CRC cell lines were used for analyses. Cell apoptosis after JMJD2B silencing was determined by flow cytometry. JC-1 fluorescence probe was applied to measure the mitochondrial outer membrane permeabilization by flow cytometry and fluorescence microscopy. Immunofluorescence was used to detect cytochrome C translocation from mitochondria to cytosol after JMJD2B silencing. The efficacy of JMJD2B silencing on the protein levels of Bcl-2 family, caspase proteins, CCAAT/enhancer binding protein homologous protein ( CHOP) and glucose-regulated protein 78 ( GRP78) were detected by Western blot. Results JMJD2B silencing induced CRC cell apoptosis via a decrease of the anti-apoptotic gene Bcl-2 family expression, leading to the translocation of Bak and Bax proteins and the promotion of mitochondrial membrane disruption, resulting in the release of cytochrome C from mitochondria and subsequent caspase-9 and caspase-3 cleavage. It also increased the amount of cleaved caspase-8 involved in the death receptor-related apoptotic pathway. Bcl-2 homology 3 interacting-domain death agonist (Bid), a specific caspase-8 substrate involved in the Fas signaling pathway, subsequently induced cleavage via caspase-8 activation. However, levels of CHOP and GRP78 remained unchanged after JMJD2B silencing. Conclusions JMJD2B silencing induced CRC cell apoptosis via both mitochondria-related and death receptor-related pathways. The cleavage of Bid activated by caspase-8 might serve as a crosstalk mediator between these two pathways in CRC.
- Subjects
COLON cancer; APOPTOSIS; CYTOMETRY; GASTROINTESTINAL motility; IMMUNOFLUORESCENCE
- Publication
Journal of Digestive Diseases, 2014, Vol 15, Issue 9, p491
- ISSN
1751-2972
- Publication type
Article
- DOI
10.1111/1751-2980.12166