Integrative Analysis of Normal Long Intergenic Non-Coding RNAs in Prostate Cancer.

Integrative Analysis of Normal Long Intergenic Non-Coding RNAs in Prostate Cancer.
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DOI:
10.1371/journal.pone.0122143
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Srinivasan S
Srinivasan S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bawa P;Zackaria S;Verma M;Gupta S;Srivatsan R;Chaudhary B;Srinivasan S

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近年来,大量的正常人体组织中的非编码RNA被发现,超过14000个长的基因间非编码RNA(lincRNA)在正常人体组织中表达。这些正常lincRNA(nlincRNA)在正常和疾病生物学中调节蛋白质编码基因的功能作用尚未确定。在这里,我们分析了两个RNA-seq数据集,包括来自不同人口统计学的12个个体的癌症和匹配的非肿瘤组织的编码基因和nlincRNA。我们发现130个nlincRNA在癌症中受到显著调节,其中127个在两个数据集中以相同的方向调节。有趣的是,根据Illumina Body Map,这些nlincRNA中的显著数量在正常前列腺组织中显示基线无效表达,但对其他组织如甲状腺,肾脏,肝脏和睾丸具有特异性。许多受调控的nlincRNA与编码基因共享基因座,这些基因在本文研究的所有癌症样品中均受到共调控或相反调控。例如,在所有癌症样品中,i)nlincRNA TCONS_00029157和相邻的肿瘤抑制因子SIK 1均被下调; ii)甲状腺特异性基因TPO附近的几种甲状腺特异性nlincRNA均被上调;和iii)TCONS_00010581(HEIH的同种型)在癌症中被下调,而相邻的EZH 2基因被上调。来自前列腺癌相关染色体基因座8 q24的几种nlincRNA与其他已知的前列腺癌相关基因(包括PCAT-1、PVT 1和PCAT-92)一起在癌症中沿着上调。我们观察到nlincRNA的上调存在显著偏差,在癌症中上调的127个中有高达118个,即使编码基因的调节偏向于下调。考虑到所有报道的癌症相关lincRNA(clincRNA)偏向于上调,我们得出结论,这种偏向可能是功能相关的。
Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant.
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影响因子: --
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