Increased expression of G9A contributes to carcinogenesis and indicates poor prognosis in hepatocellular carcinoma

被引:18
作者
Qin, Jian [1 ]
Li, Qingyun [1 ]
Zeng, Zhi [2 ]
Wu, Ping [3 ]
Jiang, Yanping [4 ]
Luo, Tao [5 ]
Ji, Xiang [3 ]
Zhang, Qiuping [3 ]
Hao, Yarong [6 ]
Chen, Lang [3 ]
机构
[1] Wuhan Univ, Renmin Hosp, Cent Lab, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Pathol, Wuhan 430060, Hubei, Peoples R China
[3] Wuhan Univ, Sch Basic Med Sci, Dept Immunol, 185 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
[4] Wuhan Univ, Renmin Hosp, Dept Gynecol & Obstet, Wuhan 430060, Hubei, Peoples R China
[5] Peking Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen, Guangdong 518036, Peoples R China
[6] Wuhan Univ, Renmin Hosp, Dept Geriatr, Wuhan 430060, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
euchromatic histone-lysine N-methyltransferase; proliferation; prognosis; LC3B; hepatocellular carcinoma; HISTONE METHYLTRANSFERASE G9A; AUTOPHAGY; METASTASIS; GENES;
D O I
10.3892/ol.2018.8572
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Euchromatic histone-lysine N-methyltransferase (G9A), the primary histone methyltransferase for histone H3 Lys(9), has been identified to be upregulated in numerous types of cancer. The aim of the present study was to analyze the clinical significance of G9A, and preliminarily explore its function in hepatocellular carcinoma (HCC). An increased expression level of G9A was demonstrated in the HCC samples and also in 5 publically available datasets. By analyzing GSE14520, it was revealed that its expression level was significantly associated with serum a-fetoprotein level of patients with HCC, and may serve as a potential prognostic indicator for patients with multinodular HCC. Bioinformatics tools were utilized to predict the potential function of G9A, and the results indicated that G9A may modulate gene sets involved in RNA processing and DNA replication. G9A inhibition may suppress cell proliferation by arresting cells in G1 phase and increasing the expression level of microtubule-associated protein light chain 3 beta (MAP1LC3B) in Huh7 and HepG2 cells. In addition, an inverse association between the expression of G9A and LC3B was demonstrated in HCC tumor samples in the publically available GSE14520 dataset, which indicated that G9A may also have the potential to regulate MAP1LC3B expression in HCC tumor tissues. The results of the present study led to hypothesis that the G9A expression level may be of assistance in diagnosing HCC, and be a potential therapeutic target for HCC. The results provided novel evidence for additional understanding of the crucial role of G9A in tumorigenesis.
引用
收藏
页码:9757 / 9765
页数:9
相关论文
共 31 条
  • [1] Autophagy: assays and artifacts
    Barth, Sandra
    Glick, Danielle
    Macleod, Kay F.
    [J]. JOURNAL OF PATHOLOGY, 2010, 221 (02) : 117 - 124
  • [2] H3K9 Histone Methyltransferase G9a Promotes Lung Cancer Invasion and Metastasis by Silencing the Cell Adhesion Molecule Ep-CAM
    Chen, Min-Wei
    Hua, Kuo-Tai
    Kao, Hsin-Jung
    Chi, Chia-Chun
    Wei, Lin-Hung
    Johansson, Gunnar
    Shiah, Shine-Gwo
    Chen, Pai-Sheng
    Jeng, Yung-Ming
    Cheng, Tsu-Yao
    Lai, Tsung-Ching
    Chang, Jeng-Shou
    Jan, Yi-Hua
    Chien, Ming-Hsien
    Yang, Chih-Jen
    Huang, Ming-Shyan
    Hsiao, Michael
    Kuo, Min-Liang
    [J]. CANCER RESEARCH, 2010, 70 (20) : 7830 - 7840
  • [3] G9a/GLP-dependent histone H3K9me2 patterning during human hematopoietic stem cell lineage commitment
    Chen, Xiaoji
    Skutt-Kakaria, Kyobi
    Davison, Jerry
    Ou, Yang-Li
    Choi, Edward
    Malik, Punam
    Loeb, Keith
    Wood, Brent
    Georges, George
    Torok-Storb, Beverly
    Paddison, Patrick J.
    [J]. GENES & DEVELOPMENT, 2012, 26 (22) : 2499 - 2511
  • [4] Enhanced Expression of EHMT2 Is Involved in the Proliferation of Cancer Cells through Negative Regulation of SIAH1
    Cho, Hyun-Soo
    Kelly, John D.
    Hayami, Shinya
    Toyokawa, Gouji
    Takawa, Masahi
    Yoshimatsu, Masanori
    Tsunoda, Tatsuhiko
    Field, Helen I.
    Neal, David E.
    Ponder, Bruce A. J.
    Nakamura, Yusuke
    Hamamoto, Ryuji
    [J]. NEOPLASIA, 2011, 13 (08): : 676 - U33
  • [5] Cancer Epigenetics: From Mechanism to Therapy
    Dawson, Mark A.
    Kouzarides, Tony
    [J]. CELL, 2012, 150 (01) : 12 - 27
  • [6] Epigenetic Regulation of Autophagy by the Methyltransferase G9a
    de Narvajas, Amaia Artal-Martinez
    Gomez, Timothy S.
    Zhang, Jin-San
    Mann, Alexander O.
    Taoda, Yoshiyuki
    Gorman, Jacquelyn A.
    Herreros-Villanueva, Marta
    Gress, Thomas M.
    Ellenrieder, Volker
    Bujanda, Luis
    Kim, Do-Hyung
    Kozikowski, Alan P.
    Koenig, Alexander
    Billadeau, Daniel D.
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2013, 33 (20) : 3983 - 3993
  • [7] Hepatocellular carcinoma
    Forner, Alejandro
    Llovet, Josep M.
    Bruix, Jordi
    [J]. LANCET, 2012, 379 (9822) : 1245 - 1255
  • [8] Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer
    Fraga, MF
    Ballestar, E
    Villar-Garea, A
    Boix-Chornet, M
    Espada, J
    Schotta, G
    Bonaldi, T
    Haydon, C
    Ropero, S
    Petrie, K
    Iyer, NG
    Pérez-Rosado, A
    Calvo, E
    Lopez, JA
    Cano, A
    Calasanz, MJ
    Colomer, D
    Piris, MA
    Ahn, N
    Imhof, A
    Caldas, C
    Jenuwein, T
    Esteller, M
    [J]. NATURE GENETICS, 2005, 37 (04) : 391 - 400
  • [9] Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators
    Fujimoto, Akihiro
    Totoki, Yasushi
    Abe, Tetsuo
    Boroevich, Keith A.
    Hosoda, Fumie
    Nguyen, Ha Hai
    Aoki, Masayuki
    Hosono, Naoya
    Kubo, Michiaki
    Miya, Fuyuki
    Arai, Yasuhito
    Takahashi, Hiroyuki
    Shirakihara, Takuya
    Nagasaki, Masao
    Shibuya, Tetsuo
    Nakano, Kaoru
    Watanabe-Makino, Kumiko
    Tanaka, Hiroko
    Nakamura, Hiromi
    Kusuda, Jun
    Ojima, Hidenori
    Shimada, Kazuaki
    Okusaka, Takuji
    Ueno, Masaki
    Shigekawa, Yoshinobu
    Kawakami, Yoshiiku
    Arihiro, Koji
    Ohdan, Hideki
    Gotoh, Kunihito
    Ishikawa, Osamu
    Ariizumi, Shun-ichi
    Yamamoto, Masakazu
    Yamada, Terumasa
    Chayama, Kazuaki
    Kosuge, Tomoo
    Yamaue, Hiroki
    Kamatani, Naoyuki
    Miyano, Satoru
    Nakagama, Hitoshi
    Nakamura, Yusuke
    Tsunoda, Tatsuhiko
    Shibata, Tatsuhiro
    Nakagawa, Hidewaki
    [J]. NATURE GENETICS, 2012, 44 (07) : 760 - U182
  • [10] The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma
    Gao, Shu-Bin
    Xu, Bin
    Ding, Li-Hong
    Zheng, Qi-Lin
    Zhang, Li
    Zheng, Qi-Fan
    Li, Shan-Hua
    Feng, Zi-Jie
    Wei, Jie
    Yin, Zhen-Yu
    Hua, Xianxin
    Jin, Guang-Hui
    [J]. JOURNAL OF HEPATOLOGY, 2014, 61 (04) : 832 - 839