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http://purl.uniprot.org/citations/30823921http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Long noncoding RNAs (lncRNAs) have been indicated to play critical roles in cancer development and progression. LncRNA HOXD cluster antisense RNA1 (HOXD-AS1) has recently been found to be dysregulated in several cancers. However, the expression levels, cellular localization, precise function and mechanism of HOXD-AS1 in colorectal carcinoma (CRC) are largely unknown.

Methods

Real-time PCR and in situ hybridization were used to detect the expression of HOXD-AS1 in CRC tissue samples and cell lines. Gain- and loss-of-function experiments were performed to investigate the biological roles of HOXD-AS1 in CRC cell line. RNA pull down, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to investigate the mechanisms underlying the functions of HOXD-AS1 in CRC.

Results

We observed that HOXD-AS1 was located in the nucleus of CRC cells and that nuclear HOXD-AS1 was downregulated in most CRC specimens and cell lines. Lower levels of nuclear HOXD-AS1 expression were associated with poor outcomes of CRC patients. HOXD-AS1 downregulation enhanced proliferation and migration of CRC cells in vitro and facilitated CRC tumourigenesis and metastasis in vivo. Mechanistic investigations revealed that HOXD-AS1 could suppress HOXD3 transcription by recruiting PRC2 to induce the accumulation of the repressive marker H3K27me3 at the HOXD3 promoter. Subsequently, HOXD3, as a transcriptional activator, promoted Integrin β3 transcription, thereby activating the MAPK/AKT signalling pathways.

Conclusion

Our results reveal a previously unrecognized HOXD-AS1-HOXD3-Integrin β3 regulatory axis involving in epigenetic and transcriptional regulation constitutes to CRC carcinogenesis and progression."xsd:string
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http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Han Y."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Wang S."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Zhao L."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Wang Y.Q."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Hu S.S."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Li T.T."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Yang M.H."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Ding Y.Q."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Li W.L."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Ou-Yang W."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/author"Ai M.L."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/name"Mol Cancer"xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/pages"31"xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/title"Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin beta3 transcriptional activating and MAPK/AKT signalling."xsd:string
http://purl.uniprot.org/citations/30823921http://purl.uniprot.org/core/volume"18"xsd:string
http://purl.uniprot.org/citations/30823921http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30823921
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