Abstract |
Emerging evidence suggests that microRNA ( miRNA) and long noncoding RNA ( lncRNA) play important roles in disease development. However, the mechanism underlying mRNA interaction with miRNA and lncRNA in idiopathic pulmonary fibrosis (IPF) remains unknown. This study presents a novel lnc-PCF that promotes the proliferation of TGF-β1-activated epithelial cells through the regulation of map3k11 by directly targeting miR-344a-5p during pulmonary fibrogenesis. Bioinformatics and in vitro translation assay were performed to confirm whether or not lnc-PCF is an actual lncRNA. RNA fluorescent in situ hybridization (FISH) and nucleocytoplasmic separation showed that lnc-PCF is mainly expressed in the cytoplasm. Knockdown and knockin of lnc-PCF indicated that lnc-PCF could promote fibrogenesis by regulating the proliferation of epithelial cells activated by TGF-β1 according to the results of xCELLigence real-time cell analysis system, flow cytometry, and western blot analysis. Computational analysis and a dual- luciferase reporter system were used to identify the target gene of miR-344a-5p, whereas RNA pull down, anti-AGO2 RNA immunoprecipitation, and rescue experiments were conducted to confirm the identity of this direct target. Further experiments verified that lnc-PCF promotes the proliferation of activated epithelial cells that were dependent on miR-344a-5p, which exerted its regulatory functions through its target gene map3k11. Finally, adenovirus packaging sh-lnc-PCF was sprayed into rat lung tissues to evaluate the therapeutic effect of lnc-PCF. These findings revealed that lnc-PCF can accelerate pulmonary fibrogenesis by directly targeting miR-344a-5p to regulate map3k11, which may be a potential therapeutic target in IPF.
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Authors | Huizhu Liu, Bingsi Wang, Jinjin Zhang, Songzi Zhang, Youlei Wang, Jie Zhang, Changjun Lv, Xiaodong Song |
Journal | Cell death & disease
(Cell Death Dis)
Vol. 8
Issue 10
Pg. e3137
(10 26 2017)
ISSN: 2041-4889 [Electronic] England |
PMID | 29072702
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MicroRNAs
- RNA, Long Noncoding
- Transforming Growth Factor beta1
- MAP Kinase Kinase Kinases
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Topics |
- Animals
- Cell Proliferation
(physiology)
- Epithelial Cells
- Idiopathic Pulmonary Fibrosis
(enzymology, genetics, metabolism, pathology)
- MAP Kinase Kinase Kinases
(metabolism)
- MicroRNAs
(metabolism)
- RNA, Long Noncoding
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Transforming Growth Factor beta1
(metabolism)
- Mitogen-Activated Protein Kinase Kinase Kinase 11
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