Overexpression of ultraconserved region 83- induces lung cancer tumorigenesis.
Overexpression of ultraconserved region 83- induces lung cancer tumorigenesis.
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DOI：
10.1371/journal.pone.0261464
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Fabbri M
中科院分区：
文献类型：
--
作者：
Vannini I;Ferracin M;Fabbri F;Fabbri M
非编码 RNA (ncRNA) 的表达在人类癌症中失调。转录的超保守区 (T-UCR) 表达参与人类癌变的长 ncRNA。 T-UCR 是非编码基因组序列，在人类、大鼠和小鼠中 100% 保守。跨物种基因组序列的保守本质上意味着重要的功能作用，因此我们考虑了 T-UCR 在肺癌中的表达。使用定制微阵列，我们分析了 T-UCR 的全局表达。在这些 T-UCR 中，观察到反义超保守元件 83 (uc.83-) 的变化最大，与邻近的非癌组织相比，该元件在人肺癌组织中表达上调。尽管uc.83-位于长基因间非蛋白编码RNA 1876 (LINC01876)基因内，但我们发现转录的uc.83-独立于LINC01876表达，并被克隆为1143-bp RNA基因。在这项研究中，功能分析证实了uc.83-对参与人类细胞生长的基因的重要影响。针对uc.83-的siRNA降低了肺癌细胞的生长，而通过过表达uc.83-RNA的载体进行上调则增加了细胞增殖。我们还表明 uc.83- 的致癌功能是由 AKT 和 ERK 1/2（肺癌细胞增殖的两个重要生物标志物）的磷酸化介导的。根据我们的研究结果，对 uc.83- 的抑制可能成为 NSCLC 的未来治疗方法，以实现同时阻断参与肺癌发生的途径。
The expression of non–coding RNAs (ncRNAs) is dysregulated in human cancers. The transcribed ultraconserved regions (T-UCRs) express long ncRNAs involved in human carcinogenesis. T-UCRs are non-coding genomic sequence that are 100% conserved across humans, rats and mice. Conservation of genomic sequences across species intrinsically implies an essential functional role and so we considered the expression of T-UCRs in lung cancer. Using a custom microarray we analyzed the global expression of T-UCRs. Among these T-UCRs, the greatest variation was observed for antisense ultraconserved element 83 (uc.83-), which was upregulated in human lung cancer tissues compared with adjacent non cancerous tissues. Even though uc.83- is located within the long intergenic non-protein coding RNA 1876 (LINC01876) gene, we found that the transcribed uc.83- is expressed independently of LINC01876 and was cloned as a 1143-bp RNA gene. In this study, functional analysis confirmed important effects of uc.83- on genes involved in cell growth of human cells. siRNA against uc.83- decreased the growth of lung cancer cells while the upregulation through a vector overexpressing the uc.83- RNA increased cell proliferation. We also show the oncogenic function of uc.83- is mediated by the phosphorylation of AKT and ERK 1/2, two important biomarkers of lung cancer cell proliferation. Based on our findings, inhibition against uc.83- could be a future therapeutic treatment for NSCLC to achieve simultaneous blockade of pathways involved in lung carcinogenesis.
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影响因子：
--
作者：
Olivieri, Michele;Ferro, Matteo;Cimmino, Amelia
通讯作者：
Cimmino, Amelia
影响因子：
3.1
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DOI：
10.1073/pnas.1011098108
发表时间：
2011-01-11
影响因子：
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通讯作者：
Patel, Tushar
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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