RESUMO
PURPOSE: Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL. METHODS: FEN1 expression was analyzed in tissues of patients with CHOL and FEN1 mutations. We observe the influence of FEN1 on cellular proliferation, migration, and invasion, as well as on DNA damage repair and glycolysis. Western blotting was performed to determine the regulatory mechanism of FEN1 in CHOL progression. RESULTS: FEN1 was highly expressed in the cancer tissues of CHOL patients. The high mutation rate of FEN1 in CHOL tissues was mainly due to the amplified repeats. FEN1 promotes the proliferation, migration, and invasion of HUCCT1 and QBC939 cells. In addition, FEN1 induced DNA damage repair and aerobic glycolysis in CHOL cells. FEN1 also promoted xenograft tumor growth in vivo. Moreover, we showed that FEN1 mediated the epithelial-mesenchymal transition (EMT) of CHOL. FEN1-mediated EMT was found to be transduced by the Wnt/ß-catenin signaling pathway. CONCLUSION: FEN1 was significantly overexpressed in CHOL tissues, and FEN1 regulates the progression of CHOL through the Wnt/ß-catenin signaling pathway.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Via de Sinalização Wnt/genética , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Linhagem Celular Tumoral , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , beta Catenina/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento CelularRESUMO
Cancer imposes a severe threat to people's health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.
