Research Papers:

Deregulation of small non-coding RNAs at the DLK1-DIO3 imprinted locus predicts lung cancer patient outcome

Katey S.S. Enfield _, Victor D. Martinez, Erin A. Marshall, Greg L. Stewart, Sonia H.Y. Kung, Jhon R. Enterina and Wan L. Lam

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Oncotarget. 2016; 7:80957-80966. https://doi.org/10.18632/oncotarget.13133

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Katey S.S. Enfield1, Victor D. Martinez1, Erin A. Marshall1, Greg L. Stewart1, Sonia H.Y. Kung1, Jhon R. Enterina1, Wan L. Lam1

1Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada

Correspondence to:

Katey S.S. Enfield, email: [email protected]

Keywords: DLK1-DIO3, imprinted locus, lung cancer, microRNA, piwi-interacting RNA

Received: September 02, 2016     Accepted: October 27, 2016     Published: November 05, 2016


Deregulation of the imprinted DLK1-DIO3 locus at chromosome 14q32.1-14q32.31 has been associated with developmental and respiratory disorders, including cancer. In lung cancer, deregulation of imprinting at DLK1-DIO3 was recently described in smokers. Deregulated expression of a microRNA (miRNA) cluster mapping to this locus was also associated with patient outcome, suggesting the importance of this locus to lung cancer disease phenotypes. The DLK1-DIO3 locus is complex, and encodes several protein-coding genes, in addition to long and short non-coding RNAs. While the role of miRNAs is established, the biological importance of another relevant class of small RNAs, PIWI-interacting RNAs (piRNAs), has not been investigated. When somatically expressed, piRNAs regulate gene transcription through DNA methylation. Interestingly, their expression patterns have been observed to be altered in cancer and correlated with patient outcome. Here, we characterize the somatic expression of piRNAs encoded at DLK1-DIO3 in two independent cohorts of lung adenocarcinoma and lung squamous cell carcinoma and investigate their associations with patient outcome. We find that the expression of piRNAs encoded at DLK1-DIO3 enhances the prognostic potential of small non-coding RNAs specific to this locus in predicting patient outcome, further emphasizing the importance of regulation at this locus in lung cancer.

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