Kwok ZH1, Roche V1, Chew XH1, Fadieieva A1, Tay Y1,2.
1Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Long noncoding RNAs (lncRNAs) constitute one of the largest classes of transcripts and have been widely implicated in various diseases such as cancer. Increasing evidence suggests that several lncRNAs are dysregulated and play critical roles in tumorigenesis. LncRNAs can be regulated by key oncogenes and tumor suppressors, adding complexity to the intricate crosstalk between protein coding genes and the non-coding transcriptome. In this study, we investigated the effect that dysregulation of the key tumor suppressor PTEN has on the non-coding transcriptome. We identified the lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) as a target of PTEN, and find that this regulation is conserved in both human and mouse, as well as with both chronic and acute PTEN dysregulation. We show that this regulation is at least in part microRNA (miRNA)-dependent, and characterize the miRNAs that may be mediating this crosstalk. In summary, we establish and characterize a non-canonical PTEN-microRNA-MALAT1 axis that regulates tumorigenesis, and describe for the first time that the MALAT1 lncRNA possesses novel tumor suppressive properties in colon and breast cancers.
Cancer; PTEN; invasion; long non-coding RNA; microRNA; migration