title: Distinct response of the hepatic transcriptome to Aflatoxin B1 induced hepatocellular carcinogenesis and resistance in rats.
abstract: Aflatoxin is a natural potent carcinogen and a major cause of liver cancer. However, the molecular mechanisms of hepatocellular carcinogenesis remain largely unexplored. In this study, we profiled global gene expression in liver tissues of rats that developed hepatocellular carcinoma (HCC) from aflatoxin B1 (AFB1) administration and those that were AFB1-resistant, as well as rats without AFB1 exposure as a control. AFB1 exposure resulted in extensive perturbation in gene expression with different functions in HCC and AFB1 resistance (AR) samples. The differentially expressed genes (DEGs) in HCC sample were enriched for cell proliferation, cell adhesion and vasculature development that largely contribute to carcinogenesis. Anti-apoptosis genes were up-regulated in HCC sample whereas apoptosis-induction genes were up-regulated in AR sample. AFB1 exposure also caused extensive alteration in expression level of lncRNAs. Among all the 4511 annotated lncRNAs, half of them were highly expressed only in HCC sample and up-regulated a group of protein-coding genes with cancer-related functions: apoptosis regulation, DNA repair, and cell cycle. Intriguingly, these genes were down-regulated by lncRNAs highly expressed in AR sample. Collectively, apoptosis is the critical biological process for carcinogenesis in response to AFB1 exposure through changes in expression level of both protein-coding and lncRNA genes.
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.|Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Jiangtu
authors.initials: J
authors.lastname: He
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, the Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ou
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.|Shanghai Key Laboratory of Signaling and Disease Research, the School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
mesh_terms: D016604:Aflatoxin B1 / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004351:Drug Resistance; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D062085:RNA, Long Noncoding / Q000187:drug effects; D051381:Rats; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D062085:RNA, Long Noncoding; D016604:Aflatoxin B1