title: Histone demethylase JMJD2B-mediated cell proliferation regulated by hypoxia and radiation in gastric cancer cell.
abstract: Histone modifying factors are functional components of chromatin and play a role in gene regulation. The expression level of JMJD2B, a histone demethylase, is notably up-regulated in cancer tissues. Upregulation of JMJD2B promotes cancer cell proliferation under hypoxic conditions through target gene expression. Here, we describe the patterns of histone methylation and JMJD2B expression under various stressed conditions, such as hypoxia and radiation, in a gastric cancer cell line. JMJD2B expression in AGS cells was actively regulated by hypoxia and radiation. Chromatin immunoprecipitation experiments demonstrated that binding of JMJD2B on the cyclin A1 (CCNA1) promoter resulted in CCNA1 upregulation under hypoxic conditions. Furthermore, we confirmed that AGS cell proliferation was directly affected by JMJD2B and CCNA1 expression by performing experiments with JMJD2B depleted cells. Interestingly, the effects of JMJD2B on cell growth under hypoxia were remarkably repressed after gamma-ray irradiation. These results suggest that JMJD2B may play a central role in gastric cancer cell growth and might constitute a novel therapeutic target to overcome hypoxia-induced radio-resistance, thereby improving the efficiency of radiation therapy.
authors.affiliation: Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea. jgkim210@gmail.com
authors.forename: Joong-Gook
authors.initials: JG
authors.lastname: Kim
authors.forename: Joo Mi
authors.initials: JM
authors.lastname: Yi
authors.forename: Seong-Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Joong-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Tae Gen
authors.initials: TG
authors.lastname: Son
authors.forename: Kwangmo
authors.initials: K
authors.lastname: Yang
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Yoo
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
mesh_terms: D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D056750:Cyclin A1 / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1; D009363:Neoplasm Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human