Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models.
Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models.
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DOI：
10.4236/jct.2013.43094
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Webster-Cyriaque J
中科院分区：
文献类型：
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作者：
Jeffers LK;Duan K;Ellies LG;Seaman WT;Burger-Calderon RA;Diatchenko LB;Webster-Cyriaque J
虽然转移相关肺腺癌转录(MALAT)-1已知在几种上皮恶性肿瘤中持续上调，但对其功能或调控知之甚少。因此，我们研究了MALAT-1表达与候选调节因子如DNA肿瘤病毒癌蛋白人乳头瘤病毒(HPV)-16 E6和E7、BK病毒T抗原（BKVTAg）、小鼠多瘤病毒中间T抗原（MPVmTAg）和肿瘤抑制基因p53和pRb之间的关系。通过抑制减法杂交（SSH）和实时逆转录酶聚合酶链反应（RT-PCR）检测，MALAT-1在人类和小鼠的病毒癌基因表达的唾液腺活检中被证明是增加的。结果还表明，当将表达癌基因的病毒质粒引入不同类型的细胞时，MALAT-1转录本和启动子活性在体外均有所增加。除了增加MALAT-1转录外，这些相同的病毒致癌基因也被证明可以抑制p53和/或pRb的功能。在p53突变或失活细胞系中，MALAT-1也被显示高度上调。我们假设MALAT-1过表达与p53去监管化之间存在相关性。总之，我们发现多瘤和乳头状瘤癌蛋白对p53的破坏似乎在MALAT-1的上调中起重要作用。因此，MALAT-1可能代表恶性肿瘤中p53解除管制的生物标志物。
Although metastasis-associated lung adenocarcinoma transcript (MALAT)-1 is known to be consistently upregulated in several epithelial malignancies, little is known about its function or regulation. We therefore examined the relationship between MALAT-1 expression and candidate modulators such as DNA tumor virus oncoproteins human papillomavirus (HPV)-16 E6 and E7, BK virus T antigen (BKVTAg), mouse polyoma virus middle T antigen (MPVmTAg) and tumor suppressor genes p53 and pRb. Using suppressive subtractive hybridization (SSH) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays, MALAT-1 was shown to be increased in viral oncongene-expressing salivary gland biopsies from humans and mice. The results also indicated that MALAT-1 transcripts and promoter activity were increased in vitro when viral oncongene-expressing plasmids were introduced into different cell types. These same viral oncogenes in addition to increasing MALAT-1 transcription have also been shown to inhibit p53 and/or pRb function. In p53 mutant or inactive cell lines MALAT-1 was also shown to be highly upregulated. We hypothesize that there is a correlation between MALAT-1 over-expression and p53 deregulation. In conclusion, we show that disruption of p53, by both polyoma and papilloma oncoproteins appear to play an important role in the up-regulation of MALAT-1. MALAT-1 might therefore represent a biomarker for p53 deregulation within malignancies.