PhD student Qi Lihua awarded travel grant from Japanese Cancer Association (JCA)

Congratulations to Qi Lihua, PhD student from Prof Daniel Tenen’s lab, for receiving a travel grant based on her submitted abstract from the Japanese Cancer Association (JCA) for the 73rd Annual Meeting held in Yokohama, Japan, from 25-27 Sep 2014.

qlh1Title: RNA-editing independent functions of ADARs on genes with extensive 3’UTR editing in hepatocellular carcinoma

Abstract: Adenosine DeAminases acting on double-stranded RNA (dsRNA) (ADARs) is a family of enzymes catalysing adenosine to inosine conversion (A-to-I editing) upon binding to dsRNA. In hepatocellular carcinoma (HCC), abnormal A-to-I editing in coding region resulting in protein recoding has been reported. However A-to-I editing is mostly enriched in 3’ untranslated regions (3’UTRs) and the associated functions remain largely unclear. Here, we investigated the regulations of ADARs on target genes with extensive 3’UTR editing, and their contributions to HCC development.

Methods: Genes with extensive 3’UTR editing were selected from published RNA-Sequencing data of HCC, and screened by a luciferase reporter assay for functional interaction with ADARs. ADARs precise regulatory mechanism was deciphered using various ADARs mutants (dsRNA binding-, deamination-depleted mutants).

Results: Among the identified targets of ADARs, METTL7A (Methyltransferase Like 7A) was found to be strongly regulated by ADARs. Surprisingly, all ADARs mutants could inhibit METTL7A expression, indicating an editing-independent regulation of ADARs. ADARs regulation of METLL7A was demonstrated to be mediated though microRNA. Moreover, METTL7A was found to be a tumor suppressor in HCC, and primary HCC tumors demonstrated reduced METTL7A expression.

Conclusion: For the first time in HCC, we discovered ADARs could regulate gene expression through an RNA editing-independent mechanism, mediated by microRNA. With the promiscuous targeting effects of microRNAs, ADARs can potentially exert profounder effects on gene expression beyond just acting as editing enzyme per se. Overall, we revealed a micro-RNA dependent regulation of ADARs contributing to HCC, opening another gate to target HCC.