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Developmental transcription factor NFIB is a putative target of oncofetal miRNAs and is associated with tumour aggressiveness in lung adenocarcinoma
Author(s) -
BeckerSantos Daiana D,
Thu Kelsie L,
English John C,
Pikor Larissa A,
Martinez Victor D,
Zhang May,
Vucic Emily A,
Luk Margaret TY,
Carraro Anita,
Korbelik Jagoda,
Piga Daniela,
Lhomme Nicolas M,
Tsay Mike J,
Yee John,
MacAulay Calum E,
Lam Stephen,
Lockwood William W,
Robinson Wendy P,
Jurisica Igor,
Lam Wan L
Publication year - 2016
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4765
Subject(s) - transcription factor , biology , microrna , adenocarcinoma , cancer research , genetics , cancer , gene
Genes involved in fetal lung development are thought to play crucial roles in the malignant transformation of adult lung cells. Consequently, the study of lung tumour biology in the context of lung development has the potential to reveal key developmentally relevant genes that play critical roles in lung cancer initiation/progression. Here, we describe for the first time a comprehensive characterization of miRNA expression in human fetal lung tissue, with subsequent identification of 37 miRNAs in non‐small cell lung cancer ( NSCLC ) that recapitulate their fetal expression patterns. Nuclear factor I/B ( NFIB ), a transcription factor essential for lung development, was identified as a potential frequent target for these ‘oncofetal’ miRNAs . Concordantly, analysis of NFIB expression in multiple NSCLC independent cohorts revealed its recurrent underexpression (in ∼40–70% of tumours). Interrogation of NFIB copy number, methylation, and mutation status revealed that DNA level disruption of this gene is rare, and further supports the notion that oncofetal miRNAs are likely the primary mechanism responsible for NFIB underexpression in NSCLC . Reflecting its functional role in regulating lung differentiation, low expression of NFIB was significantly associated with biologically more aggressive subtypes and, ultimately, poorer survival in lung adenocarcinoma patients. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.