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首页> 外文期刊>Cellular Signalling >Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression
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Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression

机译：癌症1（HIC1）中高甲基化的丧失促进肺癌进展

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摘要

Lung cancer is a leading cause of cancer mortality worldwide with dramatically increasing incidence in recent years. However, the mechanism underlying its progression remains unclear. The aim of this study was to identify the role of hypermethylated in cancer 1 (HIC1) in lung cancer development. Here we found that HIC1 expression was markedly decreased in lung cancer compared with the corresponding adjacent non-cancerous tissues. Meanwhile, overall survival (OS) of lung cancer patients was negatively related with HIC1 expression using TCGA and GEO datasets. Loss of HIC1 expression promoted cell proliferation and migration in vitro. Notable, HIC1 knock-out in Kras(G12D/+(Lox-stop-Lox))/sgHIC1 mice had remarkable effect on tumorigenesis compared with Krasc(G12D/+(Lox-stop-Lox))/sgTd control mice. Mechanistic analyses showed that ADAMTS9, DCDC2, FAM46C, ZNF883, F2R, MSH6 and PAX2 genes may be potential downstream targets; DNA repair pathway and transcriptional regulation by TP53 pathway were involved. Finally, this study reveals that HIC1 is associated with lung cancer progression and may provide an effective strategy for its treatment.
机译：肺癌是全世界癌症死亡率的主要原因，近年来急剧增加。然而，其进展的机制仍然尚不清楚。本研究的目的是确定高甲基化在肺癌发育中的癌症1（HIC1）的作用。在这里，与相应的相邻的非癌组织相比，我们发现HIC1表达在肺癌中显着降低。同时，肺癌患者的整体存活（OS）与使用TCGA和Geo数据集的HIC1表达呈负相关。 HIC1表达的丧失促进了体外细胞增殖和迁移。值得注意的是，与Krasc（G12D / +（LOX-STOP-LOX））/ SGTD对照小鼠相比，KRAS（G12D / +（LOX-STOP-LOX））/ SGHIC1小鼠的HIC1对肿瘤引发具有显着影响。机械分析表明，AdamTS9，DCDC2，FAM46C，ZNF883，F2R，MSH6和PAX2基因可能是潜在的下游靶标;涉及TP53途径的DNA修复途径和转录调节。最后，该研究表明，HIC1与肺癌进展相关，可提供有效的治疗策略。

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  • 来源
    《Cellular Signalling》 |2019年第2019期|共8页
  • 作者

    Li Yue; Yao Mengfei; Wu Tianqi; Zhang Liyan; Wang Yingying; Chen Liang; Fu Guohui; Weng Xiaoling; Wang Jianhua;

  • 作者单位

    Shanghai Jiao Tong Univ Sch Med Fac Basic Med Dept Pathol Ctr Shanghai Gen Hosp Shanghai Peoples R China;

    Fudan Univ Shanghai Canc Ctr Inst Canc Shanghai 200032 Peoples R China;

    Fudan Univ Shanghai Canc Ctr Inst Canc Shanghai 200032 Peoples R China;

    Capital Univ Med Sci Beijing Friendship Hosp Dept Neurol Beijing Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Dept Biochem &

    Mol &

    Cell Biol Shanghai Peoples R China;

    NIBS Beijing Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Fac Basic Med Dept Pathol Ctr Shanghai Gen Hosp Shanghai Peoples R China;

    Fudan Univ Shanghai Canc Ctr Inst Canc Shanghai 200032 Peoples R China;

    Fudan Univ Shanghai Canc Ctr Inst Canc Shanghai 200032 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    HIC1; Lung cancer; DNA repair pathway; Tumorigenesis;

    机译：HIC1;肺癌;DNA修复途径;肿瘤发生;

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