Abstract 4241
Background
Chemo-resistance is one of the important causes of poor prognosis of gastric cancer patients, but the exact mechanism is still not very clear. The regulation of lncRNA and miRNA and its downstream target genes has become in focus of the field.
Methods
In this study, we performed lncRNA and miRNA microarray analysis of chemo-resistant cells (SGC7901/Oxaliplatin). Then, bioinformatics analysis, TaqMan real-time PCR, western blot, luciferase reporter gene assay, RNA co-immunoprecipitation, cell proliferation and apoptosis analysis were used to explicit the lncRNA-miRNA-mRNA pathway in gastric cancer chemo-resistance. Last, nude mice were used to verify the promotion of chemo-resistance in vivo.
Results
In this study, we identified a lncRNA-GC1, which was upregulated in chemo-resistant gastric cancer tissues and cells, and a miRNA-551b-3p, which was downregulated in chemo-resistant gastric cancer tissues and cells. Firstly, miR-551b-3p can directly bind to the non-coding region of dysbindin mRNA, thereby negatively regulating the expression of dysbindin which was involved in chemotherapy resistance in gastric cancer cells. Secondly, lncRNA-GC1 promotes chemoresistance in gastric cancer by competitively binding to miR-551b-3p to facilitate dysbindin expression in vitro and in vivo. Thirdly, the expression levels of lncRNA-GC1 were positively correlated with tumor size (P = 0.002), lymph node invasion (P = 0.001) and poor platinum response (P < 0.001). Kaplan-Meier curves show that patients with high lncRNA-GC1 expression exhibit poorer overall survival compared with those with low lncRNA-GC1 expression. Multivariate analysis indicated that lncRNA-GC1 serves as an independent prognostic factor for patients with gastric cancer (P = 0.001).
Conclusions
LncRNA-GC1-miRNA-551b-3p-dysbindin signaling pathway may serve as a predictor for oxaliplatin response and a potential therapeutic target for gastric cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guo Xin.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4079 - Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy
Presenter: Gabriela Kramer-marek
Session: Poster Display session 1
Resources:
Abstract
4364 - Upregulation of sFRP3 circulating expression levels correlates survival outcomes in glioblastoma
Presenter: Gema Bruixola
Session: Poster Display session 1
Resources:
Abstract
2327 - Characterization and pre-clinical modeling of genetic aberrations in pediatric gliomas
Presenter: Itai Moshe
Session: Poster Display session 1
Resources:
Abstract
3154 - Preclinical Study of Novel Tetracyclic Small Molecule, CC12, for Brain Cancer
Presenter: Liyun Fann
Session: Poster Display session 1
Resources:
Abstract
5759 - CHLOROBRAIN phase IB trial: The addition of chloroquine, an autophagy inhibitor, to concurrent radiation and temozolomide for newly diagnosed glioblastoma
Presenter: Inge Compter
Session: Poster Display session 1
Resources:
Abstract
1382 - A Phase II Clinical Trial Evaluating the Efficacy and Safety of Apatinib Combined with dose-dense Temozolomide in Recurrent Glioblastoma
Presenter: Yong Wang
Session: Poster Display session 1
Resources:
Abstract
4407 - Phase 0 Trial of Ceritinib in Brain Metastases and Recurrent Glioblastoma
Presenter: Shwetal Mehta
Session: Poster Display session 1
Resources:
Abstract
1469 - Pembrolizumab (Pem) in recurrent high-grade glioma (HGG) patients with mismatch repair deficiency (MMRd): an observational study
Presenter: Mario Caccese
Session: Poster Display session 1
Resources:
Abstract
4217 - Outcome of high-grade gliomas (HGGs) treated into immunotherapeutic early-phase clinical trials (ieCTs): a single-center experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
5107 - Tolerability of PCV in Low Grade Glioma: a Real World Experience
Presenter: Razia Aslam
Session: Poster Display session 1
Resources:
Abstract