title: Dietary restriction protects against diethylnitrosamine-induced hepatocellular tumorigenesis by restoring the disturbed gene expression profile.
abstract: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent malignancies, worse still, there are very limited therapeutic measures with poor clinical outcomes. Dietary restriction (DR) has been known to inhibit spontaneous and induced tumors in several species, but the mechanisms are little known. In the current study, by using a diethylnitrosamine (DEN)-induced HCC mice model, we found that DR significantly reduced the hepatic tumor number and size, delayed tumor development, suppressed proliferation and promoted apoptosis. Further transcriptome sequencing of liver tissues from the DEN and the DEN accompanied with DR (DEN+DR) mice showed that DEN induced profound changes in the gene expression profile, especially in cancer-related pathways while DR treatment reversed most of the disturbed gene expression induced by DEN. Finally, transcription factor enrichment analysis uncovered the transcription factor specificity protein 1 (SP1) probably functioned as the main regulator of gene changes, orchestrating the protective effects of DR on DEN induced HCC. Taken together, by the first comprehensive transcriptome analysis, we elucidate that DR protects aginst DEN-induced HCC by restoring the disturbed gene expression profile, which holds the promise to provide effective molecular targets for cancer therapies.
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Duan
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Mohan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Yansu
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
authors.affiliation: Department of Toxicology, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001835:Body Weight; D031204:Caloric Restriction; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism*; D004052:Diethylnitrosamine / Q000009:adverse effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008297:Male; D051379:Mice; D059467:Transcriptome
chemical_list: D004052:Diethylnitrosamine