| 研究開始時の研究の概要 |
Cisplatin plus pemetrexed chemotherapy in mesothelioma patients has not improved the survival because of acquisition of chemoresistance.
Recently, lncRNAs are reported to be involved in chemoresistance to cisplatin and pemetrexed in human cancers. However, the mechanism in mesothelioma cell is not yet clear.
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| 研究実績の概要 |
Malignant mesothelioma is the aggressive cancer. Cisplatin plus pemetrexed chemotherapy in mesothelioma patients has not improved the outcome, due to acquisition of chemoresistance by malignant mesothelioma, which is not yet fully known. Recently, long non-coding RNAs are reported to be involved in chemoresistance mechanism. However, the mechanism in mesothelioma cell is not yet clear.
We analyzed gene expression of chemoresistant and chemosensitive mesothelioma using whole gene expression analysis.
After Total RNA expression, the samples were hybridized in Genechip and data obtained from the genechip scanner was analyzed with transcriptome Analysis Console.We found 2 fold differential expression of 209 noncoding gene between two groups, with 78 upregulated and 131 downregulated in chemoresistant mesothelioma.
later, we analyzed the biological function of the LINC00152, one of the long non-coding RNA expression in mesothelioma cell lines. High LINC00152 expression was associated with a poor prognosis of patients with mesothelioma. LINC00152 knockdown inhibited the proliferation, migration, and invasion of mesothelioma cell lines. These results suggest that LINC00152 is a tumor-promoting factor in mesothelioma. Direct interaction between LINC00152 and EZH2 is associated with cancer development and progression. When EZH2 expression was suppressed, LINC00152 knockdown did not suppress the proliferation, migration, and invasion of mesothelioma cells. Therefore, the tumor-promoting effect of LINC00152 in mesothelioma was dependent on EZH2 expression.
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