Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells.
Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells.
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宫颈癌细胞中vault RNA2-1-5p对p53表达和凋亡的调控
DOI：
10.18632/oncotarget.4948
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Zhang YX
中科院分区：
文献类型：
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作者：
Kong L;Hao Q;Wang Y;Zhou P;Zou B;Zhang YX
nc 886或VRNA 2 -1最近被鉴定为非编码RNA，而不是穹窿RNA或前微RNA。一些研究已经报道，前体miR-886通过其作为细胞蛋白激酶RNA激活（PKR）配体和阻遏物的活性在广泛的癌细胞中发挥肿瘤抑制作用。然而，通过对茎PCR产物进行测序，我们发现源自这种前体的microRNA，穹窿RNA 2 -1- 5 p（VTRNA 2 -1- 5 p），存在于宫颈癌细胞中。通过定量逆转录PCR（qRT-PCR），预测的VTRNA 2 - 1 - 5 p靶点的表达水平与VTRNA 2 -1- 5 p水平呈负相关。先前的结果表明，与邻近的健康组织相比，VTRNA 2 -1- 5 p在人宫颈鳞状细胞癌（CSCC）中过表达。抑制VTRNA 2 -1- 5 p增加宫颈癌细胞中Bax蛋白表达和凋亡细胞死亡。我们的研究结果表明，VTRNA 2 -1- 5 p具有与宫颈癌进展相关的致癌活性。在这里，我们报告VTRNA 2 -1- 5 p直接靶向p53表达，并在宫颈癌中作为癌基因发挥作用。VTRNA 2 -1- 5 p抑制降低宫颈癌细胞的侵袭、增殖和致瘤性，同时增加凋亡和p53表达。有趣的是，VTRNA 2 -1- 5 p抑制也增加了顺铂诱导的HeLa和SiHa细胞凋亡。在人临床宫颈癌标本中，p53低表达与VTRNA 2 -1- 5 p高表达呈正相关。此外，VTRNA 2 -1- 5 p被发现直接靶向p53的5′和3′非翻译区（UTR）。我们认为VTRNA 2 -1- 5 p是p53的直接调节因子，并提示其在宫颈癌细胞的凋亡和增殖中起重要作用。
nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated. In addition, VTRNA2-1-5p was found to directly target the 5′ and 3′ untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells.