期刊
ONCOGENE
卷 36, 期 38, 页码 5392-5406出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2017.133
关键词
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资金
- State Key Laboratory of Natural Medicines in China [SKLNMBZ201403]
- National Science and Technology Major Projects of New Drugs in China [2012ZX09103301-004, 2014ZX09508007]
- National Natural Science Foundation of China [30873073]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Central University Basic Scientific Research Business Expenses [2016ZPY009]
The long non-coding RNA, HOTTIP, has an important role in tumorigenesis. It is known that HOTTIP regulates HOX gene family; however, its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we investigated the role of HOTTIP in ESCC and observed that HOTTIP/HOXA13 was upregulated in ESCC and promoted cell proliferation and metastasis in vivo and in vitro. Interestingly, harboring a miR-30b-binding site, HOTTIP as a molecular sponge mainly regulated miR-30b level in the nucleus and modulated the repression of HOXA13 mediated by miR-30b in the cytoplasm, resulting in the positive HOTTIP/HOXA13 correlation. In addition, HOTTIP upregulated snail1 by competitively binding miR-30b, subsequently promoting epithelial-mesenchymal transition (EMT) and invasion. HOTTIP directly bound the adaptor protein WDR5 and drove histone H3 lysine 4 trimethylation and HOXA13 gene transcription in ESCC cells. In conclusion, our findings indicated that HOTTIP modulated HOXA13 at both the transcriptional and posttranscriptional levels in ESCC cells and HOTTIP-miR-30b-HOXA13 axis may serve as potential diagnostic markers or drug targets for ESCC therapies.
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