ABSTRACT
Nasopharyngeal carcinoma (NPC) is a common cancer found in the nasopharynx, which plagues countless NPC patients. MicroRNA-372 (miR-372) has been reported to be involved in various tumors. Here, we explored the important role of miR-372 in radiosensitivity, invasion, and metastasis of NPC. Microarray analysis was conducted to search the NPC-related differentially expressed genes (DEGs) and predict the miRs regulating PBK, which suggested that miR-372 could influence the development of NPC via PBK and the p53 signaling pathway. Importantly, miR-372 was observed to target PBK, thus down-regulating its expression. Then, NPC 5-8F and C666-1 cells were selected, and treated with ionization radiation and alteration of miR-372 and PBK expression to explore the functional role of miR-372 in NPC. The expression of miR-372, PBK, Bcl-2, p53, and Bax as well as the extent of Akt phosphorylation were measured. In addition, cell colony formation, cell cycle, proliferation, apoptosis, migration, and invasion were detected. At last, tumor growth and the effect of miR-372 on radiosensitivity of NPC were evaluated. Besides, over-expressed miR-372 down-regulated Bcl-2 and PBK expression and the extent of Akt phosphorylation while up-regulated the expression of p53 and Bax. Additionally, miR-372 over-expression and radiotherapy inhibited cell clone formation, proliferation, tumor growth, migration, invasion, and cell cycle entry, but promoted cell apoptosis. However, the restoration of PBK in NPC cells expressing miR-372 reversed the anti-tumor effect of miR-372 and activation of the p53 signaling pathway. In conclusion, the study shows that up-regulated miR-372 promotes radiosensitivity by activating the p53 signaling pathway via inhibition of PBK.
Subject(s)
MicroRNAs , Mitogen-Activated Protein Kinase Kinases/metabolism , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiation Tolerance/genetics , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line, Tumor , Cell Movement , Humans , Mice, Inbred BALB C , Mice, Nude , Mitogen-Activated Protein Kinase Kinases/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/radiotherapy , Signal Transduction , Tumor Suppressor Protein p53/genetics , X-RaysABSTRACT
Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Delayed diagnosis may result in progression and metastasis. Markers for early detection of RCC are lacking. The ATP-binding cassette transporter D1 (ABCD1) is located in the human peroxisome membrane. Its mutation causes X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder affecting lipid storage. The role of ABCD1 in human renal tumorigenesis was unclear. In this study, three pairs of RCC tissues were examined by cDNA microarray and data suggested that ABCD1 mRNA is downregulated. Downregulation of ABCD1 expression was confirmed by real-time PCR. ABCD1 expression was also downregulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. ABCD1 mRNA and protein expression levels assessed by immunohistochemistry in the RCC tissues were similar between genders, tumor grades, and tumor stages. Immunohistochemical assays also showed that ABCD1 expression was significantly higher in normal than in cancerous tissues (p<0.001). ABCD1 downregulation may be involved in human renal tumorigenesis.
