RESUMO
BACKGROUND/AIM: Circular RNA (circRNA) is related to gastric carcinogenesis and progression. This study explored the effects of circTCF25 on gastric cancer cell proliferation, migration, invasion, and cancer stem cell markers, as well as the potential network of circTCF25-miR and miR-149. MATERIALS AND METHODS: circTCF25 expression was detected in tissue specimens and cells by real-time quantitative reverse transcription polymerase chain reaction. Cell Counting Kit-8 and transwell assays were used to measure the effects of circTCF25 knockdown on proliferation, migration and invasion. The potential network of circTCF25 was analyzed using bioinformatic analysis. RESULTS: circTCF25 was overexpressed in human gastric cancer tissues, and a series of cancer cell lines, and was associated with shorter overall survival. Interfering with circTCF25 reduced gastric cancer cell proliferation, migration, invasion and expression of cancer stem cell markers. CircTCF25 reduced expression of miR-149, apparently by acting as a miR-149 sponge. A new circTCF25-miR-149 competitive endogenous RNA network in gastric cancer was constructed, and most core genes were associated with the malignant growth and metastatic behavior of gastric cancer. CONCLUSION: circTCF25 may have prognostic value and an oncogenic role in gastric cancer. A circTCF25-miR-149 RNA regulatory network was established which may provide novel biomarkers or potential therapeutic targets for treating gastric cancer.
Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Proliferação de Células/genética , Movimento Celular/genética , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Numerous pieces of evidence have demonstrated the functional role of miR-548 in various cancers. The expression and function of miR-548 in gastric cancer were investigated in the present study. A total of 123 gastric cancer patients were included and provided paired gastric cancer tissues and matched normal tissues. RT-qPCR was used to detect the expression of miR-548. CCK8 assay was used to evaluate cell proliferation, and Transwell assay was applied to assess cell migration and invasion. The clinical significance of miR-548 was estimated by a series of statistical analyses. miR-548 was found to be upregulated in gastric cancer, which was associated with the lymph node metastasis and TNM stage of patients. Patients with relatively high miR-548 expression possessed bad survival. miR-548 was identified as a prognostic indicator of gastric cancer. miR-548 was also found to promote the proliferation, migration, and invasion of gastric cancer. Upregulated miR-548 was involved in the progression of gastric cancer and predicted the prognosis of patients. Inhibition of miR-548 might be a novel therapeutic strategy for gastric cancer.
Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Carcinógenos , Invasividade Neoplásica/genética , Prognóstico , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
The biological activities of crocin, one of the main bioactive compounds of saffron, include anti-inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel-like factor 5 (KLF5) and hypoxia-inducible factor-1α (HIF-1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF-1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC-27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the expression of KLF5, HIF-1α, and microRNA-320 (miR-320). The miR-320/KLF5/HIF-1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF-1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF-1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF-1α, whereas miR-320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF-1α expression. Dual-luciferase reporter assay demonstrated that KLF5 was a target gene of miR-320. Crocin modulated KLF5 expression via elevation of miR-320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR-320/KLF5/HIF-1α signaling.