RESUMO
OBJECTIVE: This present study is performed to figure out the role of microRNA-136 (miR-136) in radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells through the regulation of MUC1. METHODS: Seventy-four ESCC patients were divided into radiotherapy sensitive group and radiotherapy resistance group. Colony formation assay and flow cytometry were used to test the radiosensitivity of radiotherapy resistant strain and parent strain. The expression of miR-136 between radiotherapy resistant strain and parent strain was detected by RT-qPCR, and the expression of miR-136 in Eca109 and TE-1 cells as well as Eca109-R and TE-1-R cells was detected after different doses of X-ray irradiation. Eca109 and TE-1 cells as well as Eca109-R and TE-1-R cells with overexpression of miR-136 or co-overexpression of miR-136 and MUC1 were constructed. Cell proliferation, colony formation and apoptosis was detected by CCK-8 assay, colony formation assay, and flow cytometry, respectively. RESULTS: The expression of miR-136 in ESCC tissues was lower and MUC1 mRNA and protein expression was higher than that in adjacent normal tissues. The expression of miR-136 was negatively correlated with the expression of MUC1 mRNA in ESCC. Low expression of miR-136 and high expression of MUC1 were associated with tumor size, lymph node metastasis and distant metastasis. The expression of miR-136 increased while the expression of MUC1 decreased in the radiotherapy sensitive group of ESCC patients relative to the radiotherapy resistant group. The colony formation ability of radiation resistant cell line was stronger than that of parent cell line, and the apoptosis rate showed an opposite trend. Up-regulation of miR-136 reduced the survival rate, suppressed colony formation ability and induced apoptosis of ESCC cells under irradiation, which was reversed by upregulated MUC1. CONCLUSION: This study demonstrates that up-regulation of miR-136 induces apoptosis and radiosensitivity of ESCC cells by inhibiting the expression of MUC1.
Assuntos
Apoptose/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , MicroRNAs/genética , Mucina-1/genética , Tolerância a Radiação/genética , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Raios XRESUMO
PURPOSE: Radiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child-Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT). METHODS AND MATERIALS: A total of 114 eligible patients (mean age 45 years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3±308.1) cm(3). A median dose of 53 Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6 Gy (range: 4-6 Gy). RESULTS: Patients were followed up for 1-79 months (median 19 months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5-40 Gy irradiations (V(5-40)) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V(20) were independent predictors. Using V(20) as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively. CONCLUSIONS: Our data suggest that V(20) is the unique significant dosimetric predictor for RILD risks in PLC patients with Child-Pugh Grade A cirrhosis after hypofractionated CRT.