ANALYSIS OF p53 AND miRNA EXPRESSIONS AFTER IRRADIATION IN GLIOBLASTOMA CELL LINES

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  • Glioblastoma細胞株における放射線照射後のp53とmiRNA発現解析
  • Glioblastoma サイボウカブ ニ オケル ホウシャセン ショウシャ ゴ ノ p53 ト miRNA ハツゲン カイセキ

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Abstract

Glioblastoma is a malignant brain tumor which is difficult to completely cure by surgical treatment and consequently in attempt for cure it is treated with a combination of radiotherapy and chemotherapy following surgery. Unfortunately however, these procedures are not curative for this type of tumor due to the development of resistance to anticancer drugs and radiation during treatment. P53 is a radiation-resistant factor. It plays an important role in apoptosis regulation. When cells are irradiated DNA is injured; P53 is then activated and it regulates the transcription of the target genes related to apoptosis. However, the p53 gene is defective or mutated in 50% of glioblastoma cases, thereby impairing the transcription activation capability, and thus the P53 apoptosis induction pathway does not function and apoptosis is not induced. Accordingly, the cells are less radiosensitive and show marked resistance to radiation. Apoptosis induction is an important cancer-suppressive function and it determines the sensitivity to treatments, such as chemotherapy and radiotherapy. miRNA which regulates this gene transcription has recently been reported. miRNAs are small RNAs comprised of 21-23 base-pairs. They bind to several proteins to form complexes, and bind to the N-terminal of the target mRNA for the post-transcriptional inhibition of gene expression. In this study, we analyzed the protein expression of P53, Bcl-2, Bax, and Caspase9 and miRNA expression-regulating genes involved in the P53 apoptosis pathway using a P53 mutant, T98G glioblastoma cells, and P53 wild-type A172 glioblastoma cells. Regarding miRNA, the involvement of P53-regulating mi-125b, mi-34a, mi-504, mi-380-5P, mi-885-5P, mi-145, Bax-regulating mi-21, mi-222, and mi-34a, and mi-21-regulating Bcl-2 and Caspase9 was suggested. In particular, P53 and mi-34a expressions in P53 wild-type A172 cells and Bcl-2 and mi-21 expressions in the P53 mutant type were closely involved in the P53 apoptosis induction pathway, suggesting their strong influence on the effect of radiotherapy.

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