RESUMO
BACKGROUND/AIMS: Lymph node metastasis is the primary cause of cancer-related death among patients with gastric cancer (GC), and cell division cycle 27 (CDC27) promotes the metastasis and epithelial-mesenchymal transition in many cancers. Till now, the mechanisms underlying CDC27-induced the epithelial-mesenchymal transition (EMT) of GC are still unclear. METHODS: We analyzed the expression levels of CDC27 and EMT-related biomarkers using immunohistochemistry and Western blot in 60 cases of GC tissues, and then GC cells with CDC27 shRNAs or plasmids were subjected to in vitro and in vivo assays, including CCK-8, wound healing and transwell assays. RESULTS: The CDC27 expression was obviously increased in GC tissues, and significantly correlates with EMT-related biomarkers, lymph node metastasis and poor 5-year overall survival. Additionally, in vitro and in vivo assays demonstrated that silencing of CDC27 expression effectively inhibited GC cell proliferation, invasion and metastasis. Conversely, CDC27 overexpression led to the opposite results. Finally, we demonstrated that Twist shRNA inhibited CDC27-meditated invasion and EMT of GC cells. CONCLUSION: CDC27 facilitates gastric cancer cell proliferation, invasion and metastasis via Twist-induced EMT; thus, this study offered a new therapy method for GC patients.
Assuntos
Subunidade Apc3 do Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Proteína 1 Relacionada a Twist/metabolismo , Adulto , Idoso , Animais , Subunidade Apc3 do Ciclossomo-Complexo Promotor de Anáfase/antagonistas & inibidores , Subunidade Apc3 do Ciclossomo-Complexo Promotor de Anáfase/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Proteína 1 Relacionada a Twist/antagonistas & inibidores , Proteína 1 Relacionada a Twist/genéticaRESUMO
BACKGROUND: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells. MATERIAL/METHODS: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment. RESULTS: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells. CONCLUSIONS: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.
