title: SARI, a novel target gene of glucocorticoid receptor, plays an important role in dexamethasone-mediated killing of B lymphoma cells.
abstract: Dexamethasone (Dex) has been commonly used in lymphoma and leukemia treatment, but the detailed mechanisms are not fully understood. Suppressor of AP-1 regulated by interferon (SARI) has tumor-selective growth inhibitory effect. However, it's unclear whether SARI is involved in the Dex-mediated lymphoma growth suppression. In this study, we found that Dex-treated B lymphoma tissues had a higher level of SARI. Dex repressed the growth of B lymphoma cells and upregulated SARI expression by activating glucocorticoid receptor (GR) in vitro and in vivo. Silencing of SARI attenuated the Dex-mediated growth suppression of B lymphoma cells and inhibition of AP-1 activity. Reporter assays revealed that activation of GR enhanced the transcriptional activity of SARI promoter. EMSA and ChIP assays showed that GR directly bound to the ER9 element in SARI promoter region. These results for the first time demonstrated that SARI is a novel target gene of GR, and the upregulation of SARI plays an important role in Dex's killing effect on B lymphoma cells, suggesting that SARI may serve as a novel target and a potential indicator of Dex sensitivity in B lymphoma treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Battalion 17 of Students, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: lizhang2013@aliyun.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: hefengtian06@aliyun.com.
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D050976:Basic-Leucine Zipper Transcription Factors; C569485:Batf2 protein, human; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; D003907:Dexamethasone
keywords: Dexamethasone; Gene regulation; Glucocorticoid receptor; Lymphoma; SARI