Molecular cancer, 2019-11, Vol.18 (1), p.167-167, Article 167
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis
- Ist Teil von
- Molecular cancer, 2019-11, Vol.18 (1), p.167-167, Article 167
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC. The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p. We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue. Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1476-4598eISSN: 1476-4598DOI: 10.1186/s12943-019-1097-9Titel-ID: cdi_doaj_primary_oai_doaj_org_article_90d369d8dbf6455096041ddb571fde58
- Format
- –
- Schlagworte
- Activation, Adult, Aged, AKT protein, Antigens, Argonaute 2 protein, Assaying, Biological effects, Biomarkers, Biomarkers, Tumor, Biotechnology, Cancer, Cancer metastasis, Cancer therapies, Carcinoma, Cell Line, Tumor, Cell lines, Cell Proliferation, Chromosome 3, Development and progression, Disease Progression, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, ELAV-Like Protein 1 - genetics, Female, Fluorescence, Fluorescence in situ hybridization, Fractionation, Gallbladder, Gallbladder cancer, Gallbladder Neoplasms - genetics, Gallbladder Neoplasms - metabolism, Gallbladder Neoplasms - pathology, Gene expression, Gene Expression Regulation, Neoplastic, Genes, Histone Chaperones - genetics, Histone Chaperones - metabolism, Humans, HuR, HuR protein, Immunoprecipitation, lncRNA-HGBC, Localization, Luciferase, Male, Mass spectrometry, Mass spectroscopy, Medical prognosis, Metastases, MicroRNAs - genetics, Middle Aged, miR-502-3p, Molecular modelling, Neoplasm Metastasis, Neoplasm Staging, Novels, Prognosis, Protein binding, Proteins, Proto-Oncogene Proteins c-akt - genetics, Proto-Oncogene Proteins c-akt - metabolism, Radiation therapy, Ribonucleic acid, RNA, RNA Interference, RNA polymerase, RNA, Long Noncoding - genetics, RNA-binding protein, Scientific imaging, SET, Spectroscopy, Therapeutic applications, Tissues, Tumors, Xenografts