RESUMEN
Despite advances in management, bladder cancer remains a principal cause of cancerassociated complications. Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) is dysregulated in certain types of cancer; however, limited data are available on the expression and function of TNFRSF14 in bladder cancer. In the present study, the aim was to evaluate the expression and biological functions of TNFRSF14 in bladder cancer. Firstly, the expression levels of TNFRSF14 in bladder cancer tissue were examined using The Cancer Genome Atlas (TCGA) database. Secondly, reverse transcriptionquantitative polymerase chain reaction was utilized to investigate the expression levels of TNFRSF14 in the T24, SW780 and EJM3 bladder cancer cell lines. Transfection and Cell Counting kit8 (CCK8) assay was used to evaluate whether TNFRSF14 overexpression or silencing would have an effect on cell proliferation of T24 and EJM3 cells. In addition, TNFRSF14induced apoptotic cells were identified using Annexin Vfluorescein isothiocyanate and propidium iodide staining. Western blot analysis was used to detect proteins associated with the phosphatidylinositol 3kinase pathway. According to the TCGA dataset, the expression levels TNFRSF14 were decreased in bladder cancer tissue compared with in normal control samples. Patients with bladder cancer exhibiting low expression levels of TNFRSF14 had a worse prognosis compared to those with high expression levels of TNFRSF14. Overexpression of TNFRSF14 in T24 cells led to increased apoptosis and inhibited cell proliferation in vitro. Western blotting demonstrated that TNFRSF14 overexpression increased the expression levels of caspase3p17 in T24 cells, but significantly decreased the expression levels of phosphorylated (p)protein kinase B (AKT) and P70 S6 kinase (P70). TNFRSF14 silencing in EJM3 cells enhanced cell growth, inhibited cell apoptosis, increased the expression levels of pAKT and P70, and decreased the expression levels of caspase3p17. In conclusion, TNFRSF14 may serve a tumor suppressive role in bladder cancer by inducing apoptosis and suppressing proliferation, and act as a novel prognostic biomarker for bladder cancer.
Asunto(s)
Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/genética , Humanos , Estimación de Kaplan-Meier , Fosfatidilinositol 3-Quinasa/metabolismo , Pronóstico , Miembro 14 de Receptores del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To study the radiobiological characteristic of human nasopharyngeal carcinoma cell lines CNE1 and CNE2 and the changes in expression MRN (Mre11-Rad50-Nbs1) complex in the cell lines exposed to irradiation. METHODS: CNE1 and CNE2 were irradiated by a linear accelerator. Radiobiological characteristics were detected by colony assay and MTT assay. MRN complex expression were examined by Western blot. RESULTS: Surviving fraction at 2 Gy (SF2), quasi-threshold Dose (Dq), and mean lethal dose (Do) of CNE1 were 0.56, 1.449 Gy and 1.480 Gy; SF2, Dq, and Do of CNE2 were 0.44, 0.776 Gy and 1.685 Gy, respectively. Survival fraction of CNE1 at the day 6 after 4 Gy irradiation was 0.59 and that of CNE2 was 0.79 when compared with control, with the up-regulated expressions of Rad50 in CNE1 and Mre11, Rad50 and Nbs1 in CNE2 (P < 0.05). CONCLUSIONS: CNE1 and CNE2 were sensitive to radiation, but there were radioresistance cells in CNE2. The expressions of some components of MRN complex were up-regulated to repair DNA lesions induced by radiation.