Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma

doi:10.1093/jmcb/mjx021

	Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma
	Li, Meiyi 1,2,3; Li, Chen 1,2; Liu, Wei-Xin1,4,5 ; Liu, Conghui 1,2,5; Cui, Jingru 1,2; Li, Qingrun 1,2; Ni, Hong 1,2; Yang, Yingcheng 6; Wu, Chaochao 1,2; Chen, Chunlei 1,2; Zhen, Xing 2; Zeng, Tao 1,2; Zhao, Mujun 2; Chen, Lei 6,7; Wu, Jiarui1,2,4,8 ; Zeng, Rong1,2,4 ; Chen, Luonan1,2,3,4
	2017-12
发表期刊	JOURNAL OF MOLECULAR CELL BIOLOGY
ISSN	1674-2788
卷号	9 期号:6 页码:489-503
发表状态	已发表
DOI	10.1093/jmcb/mjx021
摘要	Little is known about how chronic inflammation contributes to the progression of hepatocellular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c-myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules (a stage just before the carcinogenesis). Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocarcinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.
关键词	dynamical network biomarker inflammation-induced HCC critical transition early diagnosis high-grade dysplastic nodules tipping point
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China (NSFC)[91439103] ; National Natural Science Foundation of China (NSFC)[91529303] ; National Natural Science Foundation of China (NSFC)[30700397] ; National Natural Science Foundation of China (NSFC)[81471047] ; National Natural Science Foundation of China (NSFC)[61134013]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000425284600006
出版者	OXFORD UNIV PRESS
WOS关键词	CANCER-RELATED INFLAMMATION ; ACTIVATED RECEPTOR-ALPHA ; INDUCED LIVER-INJURY ; C-MYC ; INTEGRATED DATABASE ; CELL-PROLIFERATION ; DYSPLASTIC NODULES ; EDGE BIOMARKERS ; TRP CHANNELS ; HEPATITIS-B
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/18259
专题	生命科学与技术学院_硕士生生命科学与技术学院生命科学与技术学院_特聘教授组_曾嵘组生命科学与技术学院_特聘教授组_陈洛南组
通讯作者	Wu, Jiarui; Zeng, Rong; Chen, Luonan
作者单位	1.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, Key Lab Syst Biol,Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,Shanghai Inst Bio, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China 3.Fudan Univ, Minhang Hosp, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai, Peoples R China 7.Natl Ctr Liver Canc, Shanghai, Peoples R China 8.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Meiyi,Li, Chen,Liu, Wei-Xin,et al. Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2017,9(6):489-503.
APA	Li, Meiyi.,Li, Chen.,Liu, Wei-Xin.,Liu, Conghui.,Cui, Jingru.,...&Chen, Luonan.(2017).Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma.JOURNAL OF MOLECULAR CELL BIOLOGY,9(6),489-503.
MLA	Li, Meiyi,et al."Dysfunction of PLA2G6 and CYP2C44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma".JOURNAL OF MOLECULAR CELL BIOLOGY 9.6(2017):489-503.