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.
Highlights
Aflatoxin is a natural potent carcinogen and a major cause of liver cancer
Previous studies revealed that aflatoxin B1 (AFB1) induces mutations in the TP53 tumor suppressor gene[12,13,14], alterations in the expression of protein-coding and miRNA genes[24,25,26,27], and the synergistic effect on hepatocellular carcinogenesis of AFB1 exposure and hepatitis B virus (HBV) infection[17,18,19,20]
There are no reports about the role of Long non-coding RNAs (lncRNAs) in regulating gene expression in response to AFB1 exposure
Summary
Aflatoxin is a natural potent carcinogen and a major cause of liver cancer. the molecular mechanisms of hepatocellular carcinogenesis remain largely unexplored. AFB1 exposure 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 cancerrelated functions: apoptosis regulation, DNA repair, and cell cycle. 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 cancerrelated functions: apoptosis regulation, DNA repair, and cell cycle These genes were downregulated by lncRNAs highly expressed in AR sample. AFB1 is metabolized into the reactive oxygen species (ROS): aflatoxin-8,9-expoxide[9] This ROS can react with proteins and DNA to form adducts and cause acute toxicity (aflatoxicosis) and lesions, respectively[10,11]. The reaction of lipid peroxidation retracts a hydrogen atom from unsaturated fatty acids of membrane phospholipids, destructs cellular membrane, and results in other cytotoxic responses[16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
