title: miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells.
abstract: MicroRNAs (miRNAs) offer a new approach for molecular classification and individual therapy of human cancer due to their regulation of oncogenic pathways. In a previous report, elevated miR-375 was found in recurring gastric cancer, and it was predicted that miR-375 may be a regulator of p53 gene. However, its biological role and mechanism of actions remain unknown. In this study, we characterized the expression level of miR-375 in gastric cancer cell lines--BGC823, MGC803, SGC7901, AGS, N87, MKN45--using RT-PCR. We found that exogenous expression of miR-375 promoted the growth of AGS cells in both liquid and soft agar media. In agreement with the previous report, overexpression of miR-375 in AGS cells reduced the p53 protein expression level. A luciferase assay demonstrated that miR-375 down-regulated p53 expression through an interaction with the 3' UTR region of p53. In addition, the expression of miR-375 desensitizes cells to ionizing radiation and etoposide. Flow cytometry analyses showed that miR-375 abrogated the cell cycle arrest and apoptosis after DNA damage. These results demonstrate that miR-375 targets p53 to regulate the response to ionizing radiation and etoposide treatment.
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dong
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yan
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Jiantao
authors.initials: J
authors.lastname: Cui
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001483:Base Sequence; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D034622:RNA Interference / Q000187:drug effects* / Q000528:radiation effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide
keywords: Etoposide; Gastric cancer; Ionizing radiation; P53; miR-375