Molecular cancer, 2019-04, Vol.18 (1), p.82-16, Article 82
2019
Details
- Autor(en) / Beteiligte
- Titel
- Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy
- Ist Teil von
- Molecular cancer, 2019-04, Vol.18 (1), p.82-16, Article 82
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- SpringerLink (Online service)
- Beschreibungen/Notizen
- Gallbladder cancer is the most common biliary tract malignancy and not sensitive to chemotherapy. Autophagy is an important factor prolonging the survival of cancer cells under chemotherapeutic stress. We aimed to investigate the role of long non-coding RNAs (lncRNAs) in autophagy and chemoresistance of gallbladder cancer cells. We established doxorubicin (Dox)-resistant gallbladder cancer cells and used microarray analysis to compare the expression profiles of lncRNAs in Dox-resistant gallbladder cancer cells and their parental cells. Knockdown or exogenous expression of lncRNA combined with in vitro and in vivo assays were performed to prove the functional significance of lncRNA. The effects of lncRNA on autophagy were assessed by stubRFP-sensGFP-LC3 and western blot. We used RNA pull-down and mass spectrometry analysis to identify the target proteins of lncRNA. The drug-resistant property of gallbladder cancer cells is related to their enhanced autophagic activity. And we found a lncRNA ENST00000425894 termed gallbladder cancer drug resistance-associated lncRNA1 (GBCDRlnc1) that serves as a critical regulator in gallbladder cancer chemoresistance. Furthermore, we discovered that GBCDRlnc1 is upregulated in gallbladder cancer tissues. Knockdown of GBCDRlnc1, via inhibiting autophagy at initial stage, enhanced the sensitivity of Dox-resistant gallbladder cancer cells to Dox in vitro and in vivo. Mechanically, we identified that GBCDRlnc1 interacts with phosphoglycerate kinase 1 and inhibits its ubiquitination in Dox-resistant gallbladder cancer cells, which leads to the down-regulation of autophagy initiator ATG5-ATG12 conjugate. Our findings established that the chemoresistant driver GBCDRlnc1 might be a candidate therapeutic target for the treatment of advanced gallbladder cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1476-4598eISSN: 1476-4598DOI: 10.1186/s12943-019-1016-0Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2ba9fcc2e1aa46bdb2f529af9fce10ed
- Format
- –
- Schlagworte
- Aged, Analysis, Animals, Anthracyclines, Antibiotics, Antineoplastic - pharmacology, Antineoplastic agents, Autophagy, Autophagy - drug effects, Autophagy - genetics, Autophagy-Related Protein 12 - genetics, Autophagy-Related Protein 12 - metabolism, Autophagy-Related Protein 5 - genetics, Autophagy-Related Protein 5 - metabolism, Biliary tract, Biliary tract cancer, Breast cancer, Cancer, Cancer cells, Cancer therapies, Cancer treatment, Cell cycle, Cell Line, Tumor, Cell survival, Chemoresistance, Chemotherapy, DNA microarrays, Doxorubicin, Doxorubicin - pharmacology, Drug resistance, Drug Resistance, Neoplasm - genetics, Female, Gallbladder, Gallbladder cancer, Gallbladder Neoplasms - drug therapy, Gallbladder Neoplasms - genetics, Gallbladder Neoplasms - metabolism, Gallbladder Neoplasms - pathology, Gene expression, Gene Expression Regulation, Neoplastic, Health aspects, Hospitals, Humans, Kinases, lncRNA GBCDRlnc1, Male, Malignancy, Mass spectrometry, Mass spectroscopy, Medical prognosis, Metastasis, Mice, Mice, Nude, Microtubule-Associated Proteins - genetics, Microtubule-Associated Proteins - metabolism, Middle Aged, Non-coding RNA, Oligoribonucleotides - genetics, Oligoribonucleotides - metabolism, PGK1, Phagocytosis, Phosphoglycerate kinase, Phosphoglycerate Kinase - genetics, Phosphoglycerate Kinase - metabolism, Phosphoglycerate kinase 1, Proteins, RNA, RNA, Long Noncoding - agonists, RNA, Long Noncoding - antagonists & inhibitors, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Sensitivity enhancement, Signal Transduction, Software, Spectroscopy, Stomach cancer, Therapeutic applications, Ubiquitin, Ubiquitination, Ubiquitination - drug effects, Xenograft Model Antitumor Assays