title: Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation.
abstract: Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, National Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Fan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.forename: Yabin
authors.initials: Y
authors.lastname: Lu
authors.forename: Jiewen
authors.initials: J
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Meihong
authors.initials: M
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D015723:Gene Library; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000473:pathology*; D046228:Microarray Analysis; D034741:RNA, Small Interfering / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D050989:GATA2 Transcription Factor; D034741:RNA, Small Interfering