title: Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells.
abstract: Oncogenic KRAS, an important target for antitumor therapy, contributes to pancreatic cancer tumorigenesis, progression and maintenance. However, intracellular compensation regulation can help cells to resist the targeted therapy. Gene knockdown method such as RNAi may help to understand this intracellular regulatory system and discover novel therapeutic approach. In this study, two stable transfected cell lines were constructed through lentivirus-mediated shRNA targeting KRAS of PANC-1 cells, to investigate cell response to the knockdown of KRAS. Human whole genome microarray was then used to compare the gene expression profile. As a result, ribosomal proteins L26 and L29 (RPL26 and RPL29) were dramatically upregulated by KRAS-shRNA specifically. To identify whether RPL26 or RPL29 was critical for PANC-1 cells, siRNAs against RPL26 and RPL29 were designed and transfected in vitro. The results showed that knockdown of RPL26 or RPL29 expression significantly suppressed cell proliferation, induced cell arrest at G0/G1 phase and enhanced cell apoptosis. Reactive oxygen species (ROS) assay indicated that silencing of RPL26 or RPL29 markedly decreased the intracellular ROS generation. Our findings imply that siRNA interference against RPL26 and RPL29 is of potential value for intervention of pancreatic cancer.
authors.affiliation: School of Biotechnology, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Ge
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.forename: Minyu
authors.initials: M
authors.lastname: Luo
authors.forename: Daijie
authors.initials: D
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001779:Blood Coagulation Factors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C489216:RPL26 protein, human; C104946:RPL29 protein, human; D017382:Reactive Oxygen Species; D012269:Ribosomal Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins