RESUMO
BACKGROUND: Gastric cancer (GC) is a malignant tumor with seriously poor outcomes. Studies have shown that microRNAs (miRNAs) play an omnifarious regulatory effect in GC. However, the role of miR-3650 in the progression of GC is not well known. METHODS: In this study, miR-3650 expression and its clinical significance were determined using clinical specimens. The biological functions of miR-3650 were determined in gastric cancer cell lines through CCK-8, cell scratch, and transwell experiments. Bioinformatics predictions, combined with Western blot experiments, were employed to explore its downstream molecular targets. RESULTS: We observed that miR-3650 was overexpressed in GC specimens and most cell lines, i.e., 77.8% (MKN28, SNU1, AGS, MKN45, N87, BGC823 and SGC7901). The overexpression correlated with advanced T-stage, N-stage, M-stage, and TNM-stage. Furthermore, miR-3650 promoted the proliferation and migration of gastric cancer cells, and its overexpression promoted the PI3K-AKT-mTOR pathway and inhibited the PTEN and hippo pathways. The potassium ion signaling pathway was also involved in the biological process of miR-3650 promoting cancer. CONCLUSION: Therefore, we concluded that miR-3650/PTEN/PI3K-AKT-mTOR and miR-3650/hippo pathways are vital in the progression of GC and serve as novel targets for GC therapy.
Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Background: Gastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC. Methods: Biomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study. Results: The tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan-Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts. Conclusion: We found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.
