Deregulation of small non-coding RNAs at the DLK1-DIO3 imprinted locus predicts lung cancer patient outcome.
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.
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Katey S S
KS
Enfield
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Victor D
VD
Martinez
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Erin A
EA
Marshall
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Greg L
GL
Stewart
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Sonia H Y
SH
Kung
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Jhon R
JR
Enterina
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, B.C. V5Z 1L3, Canada.
Wan L
WL
Lam
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002135:Calcium-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007453:Iodide Peroxidase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D059467:Transcriptome; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase
DLK1-DIO3; imprinted locus; lung cancer; microRNA; piwi-interacting RNA