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RREB1-induced upregulation of the lncRNA AGAP2-AS1 regulates the proliferation and migration of pancreatic cancer partly through suppressing ANKRD1 and ANGPTL4
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 10, Iss 3, Pp 1-15 (2019)
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group UK, 2019.
-
Abstract
- Long noncoding RNAs (lncRNAs) have been reported to be involved in a variety of human diseases, including cancers. However, their mechanisms have not yet been fully elucidated. We investigated lncRNA changes that may be associated with pancreatic cancer (PC) by analyzing published microarray data, and identified AGAP2-AS1 as a relatively overexpressed lncRNA in PC tissues. qRT-PCR assays were performed to examine expression levels of AGAP2-AS1. MTT assays, colony formation assays, and EdU assays were used to determine the proliferative capacity of cells. Flow cytometry and TUNEL assays were used to study the regulation of AGAP2-AS1 in the cell cycle and apoptosis. Transwell experiments were used to study changes in cell invasion and metastasis, and a nude mouse model was established to assess the effects of AGAP2-AS1 on tumorigenesis in vivo. RNA sequencing was performed to probe AGAP2-AS1-related pathways. Subcellular fractionation and FISH assays were used to determine the distribution of AGAP2-AS1 in PC cells, and RIP and ChIP were used to determine the molecular mechanism of AGAP2-AS1-mediated regulation of potential target genes. Increased expression of AGAP2-AS1 was associated with tumor size and pathological stage progression in patients with PC. RREB1 was found to activate transcription of AGAP2-AS1 in PC cells. AGAP2-AS1 affected proliferation, apoptosis, cycle arrest, invasion, and metastasis of PC cells in vitro, and AGAP2-AS1 regulated PC proliferation in vivo. Furthermore, AGAP2-AS1 epigenetically inhibited the expression of ANKRD1 and ANGPTL4 by recruiting zeste homolog 2 (EZH2), thereby promoting PC proliferation and metastasis. In summary, our data show that RREB1-induced upregulation of AGAP2-AS1 regulates cell proliferation and migration in PC partly through suppressing ANKRD1 and ANGPTL4 by recruiting EZH2. AGAP2-AS1 represents a potential target for the diagnosis and treatment of PC in the future.
- Subjects :
- 0301 basic medicine
Cancer Research
Immunology
Mice, Nude
Muscle Proteins
Biology
medicine.disease_cause
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Nude mouse
Downregulation and upregulation
Cell Movement
Cell Line, Tumor
medicine
Angiopoietin-Like Protein 4
Animals
Humans
lcsh:QH573-671
Cell Proliferation
Mice, Inbred BALB C
Cell growth
Microarray analysis techniques
lcsh:Cytology
EZH2
Nuclear Proteins
Cell Biology
Cell cycle
Middle Aged
biology.organism_classification
Prognosis
Up-Regulation
DNA-Binding Proteins
Pancreatic Neoplasms
Repressor Proteins
030104 developmental biology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Heterografts
Female
RNA, Long Noncoding
Carcinogenesis
Carcinoma, Pancreatic Ductal
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 10
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....29bd69ec81f7902a045b6afe8b7720be