Transcriptional and posttranscriptional regulation of HOXA13 by lncRNA HOTTIP facilitates tumorigenesis and metastasis in esophageal squamous carcinoma cells.

Abstract	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.
Authors	C Lin, Y Wang, Y Wang, S Zhang, L Yu, C Guo, H Xu
Journal	Oncogene (Oncogene) Vol. 36 Issue 38 Pg. 5392-5406 (09 21 2017) ISSN: 1476-5594 [Electronic] England
PMID	28534516 (Publication Type: Journal Article)
Chemical References	Homeodomain Proteins RNA, Long Noncoding homeobox protein HOXA13 long noncoding RNA HOTTIP, human
Topics	Animals Carcinogenesis (genetics, metabolism, pathology) Carcinoma, Squamous Cell (genetics, metabolism, pathology) Cell Line, Tumor Cell Proliferation (physiology) Cell Transformation, Neoplastic Esophageal Neoplasms (genetics, metabolism, pathology) Esophageal Squamous Cell Carcinoma Female Gene Expression Regulation, Neoplastic Heterografts Homeodomain Proteins (genetics, metabolism) Humans Mice Mice, Inbred BALB C Neoplasm Metastasis Protein Processing, Post-Translational RNA, Long Noncoding (genetics, metabolism) Transcription, Genetic

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