The Landscape and Implications of Chimeric RNAs in Cervical Cancer.

The Landscape and Implications of Chimeric RNAs in Cervical Cancer.
复制标题

嵌合 RNA 在宫颈癌中的概况和意义

DOI:
10.1016/j.ebiom.2018.10.059
复制
发表时间:
2018-11
期刊:
影响因子:
11.1
通讯作者:
Li H
Li H
中科院分区:
医学1区
文献类型:
--
作者:
Wu P;Yang S;Singh S;Qin F;Kumar S;Wang L;Ma D;Li H

文献摘要

参考文献

被引文献

相似文献

基因融合和融合产品已被证明是治疗癌症的理想生物标记物和药物靶点。尽管作为癌症基因组图谱(TCGA)项目的一部分,对宫颈癌进行了全面的研究,但很少发现复发的基因融合,而且没有超过3%的频率。我们认为,通过基因间剪接产生的嵌合融合RNA代表了一种新的生物标记物和/或治疗靶点。然而,当只考虑基因组序列和DNA水平的融合时,它们将被错过。我们使用OUR和TCGA宫颈癌RNA-Seq数据集对嵌合RNA进行了广泛的数据挖掘。采用多个标准。我们从不同水平、不同角度分析了嵌合RNA的景观。随着不同过滤器的应用,嵌合RNA的格局发生了变化。鉴定出15个高频率(>10%)嵌合RNA。LHX6-NDUFA8仅在宫颈癌组织和巴氏涂片中检测到,而在正常对照中未检测到。从机制上讲,它不是由于间隙缺失,而是相邻基因之间顺式剪接的产物。另一个复发的嵌合体SLC2A11-MIF的沉默导致细胞周期停滞和细胞增殖减少。这种效应是嵌合体独有的,而不是两个亲本基因所共有的。宫颈癌中存在高频率的嵌合RNA。它们可以通过基因间剪接形成。其中一些具有作为潜在生物标志物的明确含义,或者为揭示这种疾病的生物学特性提供了新的线索。还有那个。
Gene fusions and fusion products have been proven to be ideal biomarkers and drug targets for cancer. Even though a comprehensive study of cervical cancer has been conducted as part of the Cancer Genome Atlas (TCGA) project, few recurrent gene fusions have been found, and none above 3% of frequency. We believe that chimeric fusion RNAs generated by intergenic splicing represent a new repertoire of biomarkers and/or therapeutic targets. However, they would be missed when only genome sequences and fusions at DNA level are considered. We performed extensive data mining for chimeric RNAs using both our and TCGA cervical cancer RNA-Seq datasets. Multiple criteria were applied. We analyzed the landscape of chimeric RNAs at various levels, and from different angles. The chimeric RNA landscape changed as different filters were applied. 15 highly frequent (>10%) chimeric RNAs were identified. LHX6-NDUFA8 was detected exclusively in cervical cancer tissues and Pap smears, but not in normal controls. Mechanistically, it is not due to interstitial deletion, but a product of cis-splicing between adjacent genes. Silencing of another recurrent chimera, SLC2A11-MIF, resulted in cell cycle arrest and reduced cellular proliferation. This effect is unique to the chimera, and not shared by the two parental genes. Highly frequent chimeric RNAs are present in cervical cancers. They can be formed by intergenic splicing. Some have clear implications as potential biomarkers, or for shedding new light on the biology of the disease. and the .
DOI: 10.1093/nar/gkw032
发表时间: 2016-04-07
影响因子: 14.9
作者:
Babiceanu M;Qin F;Xie Z;Jia Y;Lopez K;Janus N;Facemire L;Kumar S;Pang Y;Qi Y;Lazar IM;Li H
通讯作者: Li H
DOI: 10.1371/journal.pgen.1005001
发表时间: 2015-02
期刊: PLoS genetics
影响因子: 4.5
作者:
Qin F;Song Z;Babiceanu M;Song Y;Facemire L;Singh R;Adli M;Li H
通讯作者: Li H
DOI: 10.3324/haematol.2009.011536
发表时间: 2010-01-01
期刊: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子: --
作者:
Chase, Andrew;Ernst, Thomas;Cross, Nicholas C. P.
通讯作者: Cross, Nicholas C. P.
DOI: 10.3389/fgene.2011.00092
发表时间: 2011
影响因子: 3.7
作者:
Zaphiropoulos PG
通讯作者: Zaphiropoulos PG
DOI: 10.1126/science.1117679
发表时间: 2005-10-28
期刊: SCIENCE
影响因子: 56.9
作者:
Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
通讯作者: Chinnaiyan, AM