HOXD1 inhibits lung adenocarcinoma progression and is regulated by DNA methylation

被引:0
|
作者
Hu, Xin [1 ]
Zhang, Sijia [1 ]
Zhang, Xiaoyu [1 ]
Liu, Hongyan [2 ]
Diao, Yutao [1 ]
Li, Lianlian [1 ,3 ]
机构
[1] Shandong First Med Univ, Sch Clin & Basic Med Sci, Dept Immunol, Jinan 250117, Shandong, Peoples R China
[2] Shandong First Med Univ, Jinan Cent Hosp, Res Ctr Basic Med, Jinan 250013, Shandong, Peoples R China
[3] Shandong First Med Univ, Dept Oncol, Shandong Prov Hosp, 324 Jingwu Weiqi Rd, Jinan 250021, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
homeobox D1; lung cancer; DNA methylation; DNA methyltransferase; biomarker; BONE MORPHOGENETIC PROTEINS; CANCER; EXPRESSION; GENES; PROLIFERATION; PROMOTER; ROLES;
D O I
10.3892/or.2024.8832
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The homeobox (HOX) gene family encodes a number of highly conserved transcription factors and serves a crucial role in embryonic development and tumorigenesis. Homeobox D1 (HOXD1) is a member of the HOX family, whose biological functions in lung cancer are currently unclear. The University of Alabama at Birmingham Cancer data analysis Portal of HOXD1 expression patterns demonstrated that HOXD1 was downregulated in lung adenocarcinoma (LUAD) patient samples compared with adjacent normal tissue. Western blotting analysis demonstrated low HOXD1 protein expression levels in lung LUAD cell lines. The Kaplan-Meier plotter database demonstrated that reduced HOXD1 expression levels in LUAD correlated with poorer overall survival. Meanwhile, an in vitro study showed that HOXD1 overexpression suppressed LUAD cell proliferation, migration and invasion. In a mouse tumor model, upregulated HOXD1 was demonstrated to inhibit tumor growth. In addition, targeted bisulfite sequencing and chromatin immunoprecipitation assays demonstrated that DNA hypermethylation occurred in the promoter region of the HOXD1 gene and was associated with the action of DNA methyltransferases. Moreover, upregulated HOXD1 served as a transcriptional factor and increased the transcriptional expression of bone morphogenic protein (BMP)2 and BMP6. Taken together, the dysregulation of HOXD1 mediated by DNA methylation inhibited the initiation and progression of LUAD by regulating the expression of BMP2/BMP6.
引用
收藏
页数:13
相关论文
共 50 条
  • [21] Identification of Prognostic DNA Methylation Signatures in Lung Adenocarcinoma
    Wang, Pengli
    Xu, Gaoran
    Gao, Erji
    Xu, Yong
    Liang, Leilei
    Jiang, Gening
    Duan, Liang
    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2022, 2022
  • [22] High DNA methylation in lung adenocarcinoma with a micropapillary pattern
    Ito, Yuki
    Matsusaka, Keisuke
    Usui, Genki
    Seki, Motoaki
    Fukuyo, Masaki
    CANCER SCIENCE, 2022, 113 : 840 - 840
  • [23] A Diagnostic Panel of DNA Methylation Biomarkers for Lung Adenocarcinoma
    Shen, Nan
    Du, Jun
    Zhou, Hui
    Chen, Nan
    Pan, Yi
    Hoheisel, Jorg D.
    Jiang, Zonghui
    Xiao, Ling
    Tao, Yue
    Mo, Xi
    FRONTIERS IN ONCOLOGY, 2019, 9
  • [24] DNA methylation profiling in lung adenocarcinoma cell lines
    Heller, Gerwin
    Ziegler, Barbara
    Gsur, Andrea
    Zielinski, Christoph
    Zoechbauer-Mueller, Sabine
    CANCER RESEARCH, 2009, 69
  • [25] A prediction panel with DNA methylation biomarkers for lung adenocarcinoma
    Shen, N.
    Pan, Y.
    Mo, X.
    ANNALS OF ONCOLOGY, 2018, 29
  • [26] Adenocarcinoma progression in Barrett Oesophagus, association with DNA methylation changes
    Valero Torres, A.
    Hoerndler, C.
    Chueca, E.
    Lozano, J. J.
    Garcia Gonzalez, M. A.
    Strunk, M.
    Lanas, A.
    Roche, B.
    Gurrea Vidal, N.
    Torrecilla Idoipe, N.
    Piazuelo, E.
    VIRCHOWS ARCHIV, 2014, 465 : S147 - S147
  • [27] Association between SOX gene family expression, DNA methylation, and miRNA regulation in lung adenocarcinoma progression
    Wang, Haidao
    Hu, Yiming
    Lu, Haibin
    Wu, Zhijie
    Zhang, Yixiang
    DISCOVER ONCOLOGY, 2025, 16 (01)
  • [28] PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity
    Shuang Wang
    Ximeng Liu
    Ting Zhou
    Jinling Li
    Ying Lin
    Anni Zhou
    Jiamin Huang
    Jingjing Zhao
    Junchao Cai
    Xiuyu Cai
    Yongbo Huang
    Xu Li
    Cellular Oncology, 2023, 46 : 195 - 209
  • [29] PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity
    Wang, Shuang
    Liu, Ximeng
    Zhou, Ting
    Li, Jinling
    Lin, Ying
    Zhou, Anni
    Huang, Jiamin
    Zhao, Jingjing
    Cai, Junchao
    Cai, Xiuyu
    Huang, Yongbo
    Li, Xu
    CELLULAR ONCOLOGY, 2023, 46 (01) : 195 - 209
  • [30] SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation
    Wang Jia-lei
    Lu Fan-Zhen
    Shen Xiao-yong
    Wu Yun
    Zhao Li-ting
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 455 (3-4) : 229 - 233