HAfTs are novel lncRNA transcripts from aflatoxin exposure

Area of Science:

• Toxicogenomics
• Molecular Biology
• Bioinformatics

Background:

• The liver transcriptome offers insights into precancer biology.
• Aflatoxin B1 (AFB1) is a known carcinogen that induces liver tumors.
• Early detection of molecular changes preceding tumor onset is crucial for understanding carcinogenesis.

Purpose of the Study:

• To identify and characterize novel transcripts in rat liver exposed to AFB1.
• To investigate the potential of these novel transcripts as early biomarkers for chemical hepatocarcinogens.
• To explore the evolutionary conservation and potential functions of identified transcripts.

Main Methods:

• RNA-sequencing (RNA-Seq) analysis of liver RNA from male rats exposed to AFB1.
• PCR-cloning and rapid amplification of cDNA ends (RACE) for transcript identification and validation.
• Sanger sequencing for detailed transcript characterization.
• BLAST alignments and genomic synteny analysis for homology assessment.

Main Results:

• Over 1,000 differentially expressed transcripts were identified, including novel, unannotated Hepatic Aflatoxin Transcripts (HAfTs).
• HAfTs were predominantly long non-coding RNAs (lncRNAs) (>200nt) with no apparent long open reading frames.
• Six rat HAfT transcripts showed homology in mouse and human genomes, with some loci previously unannotated.
• Alternative splice variants and refinements in exon sequences were observed compared to initial predictions.
• Potential coregulatory roles were suggested by the adjacent orientation of HAfTs to known coding genes.

Conclusions:

• Novel, differentially expressed lncRNAs (HAfTs) were identified in rat livers following AFB1 exposure, preceding tumor development.
• These HAfTs represent a new class of molecules potentially useful as early biomarkers for genotoxic chemical exposure.
• Further characterization of HAfTs could elucidate their roles in hepatocarcinogenesis and provide sensitive markers for early detection.