title: Inhibition of hypoxia inducible factor 1α by siRNA-induced apoptosis in human retinoblastoma cells.
abstract: Hypoxia, which activates the hypoxia inducible factor 1α (HIF-1α), is an essential feature of retinoblastoma (RB) and contributes to poor prognosis and resistance to conventional therapy. In this study, the effect of HIF-1α knockdown by small interfering RNA (siRNA) on cell proliferation, apoptosis, and apoptotic pathways of human Y-79 RB cells was first investigated. Exposure to hypoxia induced the increased expression of HIF-1α both in mRNA and protein levels. Then, knockdown of HIF-1α by siRNAHIF-1α resulted in inhibition of cell proliferation and induced cell apoptosis in human Y-79 RB cells under both normoxic and hypoxic conditions, with hypoxic conditions being more sensitive. Furthermore, knockdown of HIF-1α could enhance hypoxia-induced slight increase of Bax/Bcl-2 ratio and activate caspase-9 and caspase-3. These results together indicated that suppression of HIF-1α expression may be a promising strategy for the treatment of human RB in the future.
authors.affiliation: Department of Ophthalmology, No. 411 Hospital of CPLA, Shanghai, 200081, People's Republic of China. gaoyu7607@gmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Jing
authors.forename: Rongrong
authors.initials: R
authors.lastname: Ge
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D012175:Retinoblastoma; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Hypoxia Inducible Factor 1α; Y-79 Retinoblastoma Cells; siRNA