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Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin β3 transcriptional activating and MAPK/AKT signalling

Yang, Min-Hui ; Zhao, Li ; Wang, Lan ; Ou-Yang, Wen ; Hu, Sha-Sha ; Li, Wen-Lu ; Ai, Mei-Ling ; Wang, Yi-Qing ; Han, Yue ; Li, Ting-Ting ; Ding, Yan-Qing ; Wang, Shuang

Molecular cancer, 2019-03, Vol.18 (1), p.31-16, Article 31 [Periódico revisado por pares]

England: BioMed Central

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Título:
Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin β3 transcriptional activating and MAPK/AKT signalling
Autor: Yang, Min-Hui ; Zhao, Li ; Wang, Lan ; Ou-Yang, Wen ; Hu, Sha-Sha ; Li, Wen-Lu ; Ai, Mei-Ling ; Wang, Yi-Qing ; Han, Yue ; Li, Ting-Ting ; Ding, Yan-Qing ; Wang, Shuang
Assuntos: AKT protein ; Antisense RNA ; Biotechnology ; Carcinogenesis ; Cell adhesion & migration ; Cell lines ; Cell migration ; Cell proliferation ; Chromatin ; Colorectal cancer ; Colorectal carcinoma ; Gene expression ; Gene regulation ; HOXD-AS1 ; HOXD3 ; Hybridization ; Immunoprecipitation ; Investigations ; lncRNA ; Localization ; MAP kinase ; Metastases ; Metastasis ; Migration ; Nuclei (cytology) ; Ovarian cancer ; PRC2 ; Ribonucleic acid ; RNA ; Signal transduction ; Transcription ; Tumors
É parte de: Molecular cancer, 2019-03, Vol.18 (1), p.31-16, Article 31
Descrição: 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. 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. 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. 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.
Editor: England: BioMed Central
Idioma: Inglês

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Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin β3 transcriptional activating and MAPK/AKT signalling

Yang, Min-Hui ; Zhao, Li ; Wang, Lan ; Ou-Yang, Wen ; Hu, Sha-Sha ; Li, Wen-Lu ; Ai, Mei-Ling ; Wang, Yi-Qing ; Han, Yue ; Li, Ting-Ting ; Ding, Yan-Qing ; Wang, Shuang

England: BioMed Central

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