Integrative expression analysis identifies a novel interplay between CFTR and linc-SUMF1-2 that involves CF-associated gene dysregulation
| Autor: | Keiko Ueno-Shuto, Jian Dong Li, Yukihiro Tasaki, Yuka Eto, Mary Ann Suico, Shingo Suzuki, Tsuyoshi Shuto, Hirofumi Nohara, Shunsuke Kamei, Taisei Kawakami, Dieter C. Gruenert, Kasumi Maruta, Haruka Fujikawa, Hirofumi Kai, Ryunosuke Nakashima |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cystic Fibrosis Biophysics Regulator Cystic Fibrosis Transmembrane Conductance Regulator Bronchi Biology Biochemistry Cystic fibrosis Cell Line Transcriptome 03 medical and health sciences 0302 clinical medicine medicine CXCL10 Humans Molecular Biology Gene RNA Epithelial Cells Cell Biology respiratory system medicine.disease Transmembrane protein Cell biology CTGF 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis RNA Long Noncoding |
| Zdroj: | Biochemical and biophysical research communications. 509(2) |
| ISSN: | 1090-2104 |
| Popis: | Cystic fibrosis transmembrane regulator (CFTR) is a cyclic AMP-dependent Cl- channel, and its dysfunction, due to CFTR gene mutations, causes the lethal inherited disorder cystic fibrosis (CF). To date, widespread dysregulation of certain coding genes in CF airway epithelial cells is well studied and considered as the driver of pulmonary abnormality. However, the involvement of non-coding genes, novel classes of functional RNAs with little or no protein-coding capacity, in the regulation of CF-associated gene dysregulation is poorly understood. Here, we utilized integrative analyses of human transcriptome array (HTA) and characterized 99 coding and 91 non-coding RNAs that are dysregulated in CFTR-defective CF bronchial epithelial cell line CFBE41o-. Among these genes, the expression level of linc-SUMF1-2, an intergenic non-coding RNA (lincRNA) whose function is unknown, was inversely correlated with that of WT-CFTR and consistently higher in primary human CF airway epithelial cells (DHBE-CF). Further integrative analyses under linc-SUMF1-knockdown condition determined MXRA5, SEMA5A, CXCL10, AK022877, CTGF, MYC, AREG and LAMB3 as both CFTR- and linc-SUMF1-2-dependent dysregulated gene sets in CF airway epithelial cells. Overall, our analyses reveal linc-SUMF1-2 as a dysregulated non-coding gene in CF as well as CFTR-linc-SUMF1-2 axis as a novel regulatory pathway involved in CF-associated gene dysregulation. |
| Databáze: | OpenAIRE |
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