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An integrative transcriptome analysis reveals a functional role for thyroid transcription factor‐1 in small cell lung cancer
Author(s) -
Horie Masafumi,
Miyashita Naoya,
Mattsson Johanna Sofia Margareta,
Mikami Yu,
Sandelin Martin,
Brunnström Hans,
Micke Patrick,
Nagase Takahide,
Saito Akira
Publication year - 2018
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.5109
Subject(s) - transcription factor , biology , transcriptome , cancer research , microrna , neuroendocrine differentiation , transcriptional regulation , downregulation and upregulation , lung cancer , thyroid , thyroid transcription factor 1 , cancer , gene , medicine , gene expression , genetics , prostate cancer
Small cell lung cancer (SCLC) is a neuroendocrine tumour that exhibits rapid growth and metastatic spread. Although SCLC represents a prototypically undifferentiated cancer type, thyroid transcription factor‐1 (TTF‐1, gene symbol NKX2‐1 ), a master regulator for pulmonary epithelial cell differentiation and lung morphogenesis, is strongly upregulated in this aggressive cancer type. The aim of this study was to evaluate a functional role for TTF‐1 in SCLC. We demonstrated that achaete‐scute complex homolog 1 (ASCL1), an essential transcription factor for neuroendocrine differentiation, positively regulated TTF‐1 in SCLC cell lines. Subsequently, we described genes and microRNAs (miRNAs) that were possibly controlled by TTF‐1 and identified nuclear factor IB (NFIB), a recently characterised driver of SCLC progression, as a transcriptional target of TTF‐1. Our findings shine light on a regulatory axis in SCLC consisting of ASCL1/TTF‐1/NFIB that potentially contributes to the tumourigenesis of SCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.