title: PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs.
abstract: PES1 (also known as Pescadillo), a nucleolar protein, was involved in biogenesis of ribosomal RNA. Up-regulation of PES1 has been documented in some human cancers, indicating that PES1 may play some crucial roles in tumorigenesis. In our previous study, it was found that silencing of PES1 resulted in decreased proliferation of colorectal cancer cells. We also noticed that depletion of PES1 altered expression profiles of diverse genes. In the present study, we validated the expression changes of a subset of genotoxic stress-related genes in PES1-silenced HCT116 cells by quantitative RT-PCR. The steady and etoposide-induced phosphorylated H2AX (γ-H2AX) were higher in PES1-silenced cells than in control cells. Besides, etoposide-induced γ-H2AX persisted longer in PES1-silenced cells after removing the etoposide. Next, results of comet assay revealed decreased DNA repair after PES1-ablation. PES1-ablated cells were more sensitive to chemotherapeutic agents, which could be reversed by reconstitution with exogenous PES1. Furthermore, deletion of PES1 diminished steady and DNA damage-induced levels of nuclear RAD51. Our results uncover a potential role of PES1 in chemoresistance by regulating DNA damage response in colorectal cancer cells.
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors: Wei
authors: W
authors: Xie
authors: Like
authors: L
authors: Qu
authors: Lin
authors: L
authors: Meng
authors: Caiyun
authors: C
authors: Liu
authors: Jian
authors: J
authors: Wu
authors: Chengchao
authors: C
authors: Shou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C484463:PES1 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase