RESUMO
OBJECTIVES: Although great progress has made in gastric cancer (GC) in the past years, the overall 5-year survival rate remains to be low for advanced GC patients. A recent study showed that PLAGL2 was increased in GC and enhanced the proliferation and metastasis of GC. Nevertheless, the underlying mechanism still needs to be investigated. METHODS: Gene and protein expressions were assessed using RT-qPCR and western blot. The migration, proliferation and invasion of GC cells were examined using scratch assay, CCK-8 assay and Transwell assay, respectively. ChIP-PCR, dual-luciferase assay, RIP-qPCR and CoiP were utilized to confirm the interaction among PLAGL2, UCA1, miR-145-5p and YTHDF1 as well as METTL3, YTHDF1 and eEF-2. A mouse xenograft model was used utilized to further confirm the regulatory network. RESULTS: PLAGL2 bound to the upstream promoter of UCA1, which regulated YTHDF1 by sponging miR-145-5p. METTL3 can mediate the m6A modification level of Snail. YTHDF1 recognized m6A-modified Snail by interacting with eEF-2 and thus promoted Snail expression, which eventually induced epithelial-mesenchymal transition (EMT) in GC cells and metastasis of GC. CONCLUSIONS: Overall, our study demonstrates that PLAGL2 enhances Snail expression and GC progression via the UCA1/miR-145-5p/YTHDF1 axis, suggesting that PLAGL2 may become a therapeutic target for GC treatment.
Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Metiltransferases/genética , Metiltransferases/metabolismo , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Introduction: The malacoplakia of the bladder is a rare chronic acquired infection- associated granulomatous disease and even less common in combination with urinary stones. Case Presentation: We report the case of a 58-year-old female patient with malacoplakia of the bladder combined with renal calculi. The patient was admitted to the hospital with bilateral low back pain for one month and space-occupying lesions of the bladder for three days. Preoperative imaging suggested space-occupying lesions of the bladder: high probability of bladder cancer. Following the anti-infection treatment, the transurethral electrodesiccation was performed on the space-occupying lesions of the bladder. Pathological examination confirmed the diagnosis of malacoplakia of the bladder. Left-sided percutaneous nephrolithotomy was performed electively to remove the predisposing factors of infection. After the operation, the patient continued to receive anti-infection treatment for two months. The patient had a good prognosis in the six-month follow-up. Conclusions: Malacoplakia of the bladder is easily misdiagnosed as bladder cancer before operation, and the diagnosis depends on pathological diagnosis. Complete removal of urinary calculi, infection and other inducing factors, is beneficial to the treatment of malacoplakia of the bladder.