Down-regulation of RNA editing in pediatric astrocytomas - ADAR2 editing activity inhibits cell migration and proliferation
Down-regulation of RNA editing in pediatric astrocytomas - ADAR2 editing activity inhibits cell migration and proliferation
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DOI：
10.1074/jbc.m708316200
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发表时间：
2008-03-14
影响因子：
4.8
通讯作者：
Gallo, Angela
中科院分区：
文献类型：
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作者：
Cenci, Caterina;Barzotti, Rita;Gallo, Angela
由于转录后事件的改变可能导致癌症的出现和/或进展，我们研究了由阿达尔（作用于RNA的腺苷脱氨酶）酶催化的RNA编辑是否在儿科星形细胞瘤中发生改变。我们发现ADAR 2编辑活性的降低似乎与儿童恶性肿瘤的分级相关。尽管肿瘤组织中ADAR 2编辑活性丧失，但与其特定对照组织相比，高级别星形细胞瘤的ADAR 2表达没有改变。然而，高表达水平的ADAR 1和ADAR 3被发现在肿瘤中相比，在大脑的同一区域解剖的正常组织。我们在三个星形细胞瘤细胞系（U118，A172，U87）中重新引入ADAR 2或ADAR 2的失活版本。“回复的”编辑状态对于如通过增殖、细胞周期和迁移测定所测量的细胞恶性行为的显著降低是必要的和足够的。我们发现，在星形细胞瘤中发现的ADAR 1水平升高确实干扰了ADAR 2特异性编辑活性。此外，我们表明，内源性ADAR 1可以形成异源二聚体与ADAR 2在星形胶质细胞。
Since alterations in post-transcriptional events can contribute to the appearance and/ or progression of cancer, we investigated whether RNA editing, catalyzed by the ADAR ( adenosine deaminases that act on RNA) enzymes, is altered in pediatric astrocytomas. We find a decrease in ADAR2 editing activity that seems to correlate with the grade of malignancy in children. Despite the loss of ADAR2 editing activity in tumor tissues, the high grade astrocytomas do not exhibit alterations in ADAR2 expression when compared with their specific control tissues. However, high expression levels of ADAR1 and ADAR3 were found in tumors when compared with normal tissues dissected in the same area of the brain. We reintroduced either ADAR2 or the inactive version of ADAR2 in three astrocytoma cell lines ( U118, A172, U87). The "reverted" editing status is necessary and sufficient for a significant decrease in cell malignant behavior as measured by proliferation, cell cycle, and migration assays. We show that elevated levels of ADAR1, as found in astrocytomas, do indeed interfere with ADAR2 specific editing activity. Furthermore, we show that the endogenous ADAR1 can form heterodimers with ADAR2 in astrocytes.