RESUMO
Oral squamous cell carcinoma (OSCC) is one of the most aggressive and lethal malignancies affecting the head and neck region with a general 5-year survival rate about 50%. Long non-coding RNAs (lncRNAs) are believed to participate in diverse biological processes and are emerging as convenient and minimally invasive diagnostic/prognostic/therapeutic markers. The aim of this study was to explore CEBPA-AS1 role and mechanism in OSCC tumorigenesis. In this study, CEBPA-AS1 localized in the cytoplasm and the peri-nuclear cellular compartment functioning as a potential oncogene up-regulated in OSCC was correlated with poor differentiation, lymph node metastasis and high clinical stage, which made it considered to be a prognostic biomarker. Silence of CEBPA-AS1 inhibited OSCC cells proliferation and induced cells apoptosis, migration and invasion by targeting CEBPA and via a novel pathway CEBPA/Bcl2. Our findings provided the first evidence for the lncRNA CEBPA-AS1 regulatory network in OSCC tumorigenesis, which might be helpful to improve the effects of clinical treatment in OSCC.
Assuntos
Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Apoptose/genética , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Citoplasma/genética , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Queratinócitos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/citologia , Mucosa Bucal/patologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , Regulação para CimaRESUMO
Oral squamous cell carcinoma is a common and lethal malignancy affecting the head and neck region. CCAT2 (colon cancer-associated transcript 2) gene is affiliated with long non-coding RNAs, which are often found to have important regulatory roles in cancers. This study aims to assess the expression and clinical significance of CCAT2 gene, identify its malignant biological behaviors, and explore the possible mechanisms in oral squamous cell carcinoma. CCAT2 expression was detected by quantitative real-time polymerase chain reaction, and its relationship with clinical factors was assayed using the Kaplan-Meier survival curve. The biological behaviors of CCAT2 and its potential mechanisms in oral squamous cell carcinoma were explored by the combined use of CCAT2 knockdown technology and the Wnt/ß-catenin pathway agonist lithium chloride (LiCl). Our results showed that CCAT2 functioning as a potential oncogene was upregulated in oral squamous cell carcinoma. CCAT2 with high expression level was correlated with poor differentiation, higher T stage, and clinical stage, which made CCAT2 to be a prognostic biomarker in oral squamous cell carcinoma. LiCl-activated Wnt/ß-catenin signaling pathway could partly restore the CCAT2-mediated malignant biological behaviors of oral squamous cell carcinoma cells by suppressing ß-catenin, CCND1, and MYC and activating glycogen synthase kinase 3 beta expression. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for oral squamous cell carcinoma, thereby improve the effects of clinical treatment in patients.