RESUMO
BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.
Assuntos
Fibronectinas , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-myc , RNA Circular , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Proteólise , Camundongos Nus , Sequência de Bases , Movimento Celular/genética , Feminino , CamundongosRESUMO
BACKGROUND: Breast cancer is one of the most common type of cancers worldwide and remains a critical health issue. Although there are numerous treatment options for advanced metastatic breast cancer, the results are not satisfactory, particularly for triple-negative breast cancer. New treatment modalities need to be explored. CASE PRESENTATION: We present the case of a breast cancer patient with multiple metastases who achieved a good response and tolerance to the combination treatment of utidelone plus capecitabine. After being treated with 10 cycles of combined treatment, the patient is now in a good general condition with a progression-free survival time of 10 months. CONCLUSION: To our knowledge, this is the first report of utidelone plus capecitabine successfully treating a patient with heavily pretreated metastatic breast cancer. This combined treatment offers a new option for patients with multi-drug resistant breast cancer.