Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease

Qiu, Wenying; Guo, Xiaoyun; Lin, Xiaoxiao; Yang, Qian; Zhang, Wanying; Zhang, Yong; Zuo, Lingjun; Zhu, Yong; Li, Chiang‐Shan R.; Ma, Chao; Luο, Xingguang

doi:10.1016/j.neurobiolaging.2017.05.020

Cited by 79 publications

(58 citation statements)

References 57 publications

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“…Recent evidence suggests that piRNAs are abundant in the brain (Mani and Juliano 2013; Rajasethupathy et al 2012; Lee et al 2011; Sharma et al 2001; Perrat et al 2013; Yan et al 2011; Ghildiyal et al 2008; Dharap et al 2011; Peng and Lin 2013; Zuo et al 2016b; Qiu et al 2017). piRNAs may regulate the mRNAs and translation of the proximate risk genes (Grivna et al 2006) or interact with neurotransmitters in brains (Ross et al 2014; Rajasethupathy et al 2012), and thus may play roles in brain disorders.…”

Section: Discussionmentioning

confidence: 99%

“…These risk SNPs were genotyped in our own small cohort (6 AD and 6 controls) to replicate the SNP-AD association (Qiu et al 2017), which was approved by the ethics committee of The Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences.…”

Section: Summary Of Materials and Methods (Much Detailed In The Sumentioning

confidence: 99%

“…For the piRNA expression, the transcriptome-wide piRNAs in human brains of our small Chinese cohort (6 AD and 6 controls; see above) were studied (Qiu et al 2017) and the trans -regulatory effects of these SNPs on the piRNAs were examined. Furthermore, the expression of mRNAs and proteins encoding by these risk genes were examined in multiple brain regions in multiple independent European and American cohorts, the correlations between their mRNA expression and the APOE expression in brain were tested, and the most possible phenotype that these risk genes can predict for was explored using pathway/network analysis.…”

Section: Summary Of Materials and Methods (Much Detailed In The Sumentioning

confidence: 99%

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Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

et al. 2017

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Genome-wide association studies (GWASs) have reported numerous associations between risk variants and Alzheimer’s disease (AD). However, these associations do not necessarily indicate a causal relationship. If the risk variants can be demonstrated to be biologically functional, the possibility of a causal relationship would be increased. In this article, we reviewed all of the published GWASs to extract the genome-wide significant (p<5×10−8) and replicated associations between risk variants and AD or AD-biomarkers. The regulatory effects of these risk variants on the expression of a novel class of non-coding RNAs (piRNAs) and protein-coding RNAs (mRNAs), the alteration of proteins caused by these variants, the associations between AD and these variants in our own sample, the expression of piRNAs, mRNAs and proteins in human brains targeted by these variants, the expression correlations between the risk genes and APOE, the pathways and networks that the risk genes belonged to, and the possible long non-coding RNAs (LncRNAs) that might regulate the risk genes were analyzed, to investigate the potential biological functions of the risk variants and explore the potential mechanisms underlying the SNP-AD associations. We found replicated and significant associations for AD or AD-biomarkers, surprisingly, only at 17 SNPs located in 11 genes/snRNAs/LncRNAs in eight genomic regions. Most of these 17 SNPs enriched some AD-related pathways or networks, and were potentially functional in regulating piRNAs and mRNAs; some SNPs were associated with AD in our sample, and some SNPs altered protein structures. Most of the protein-coding genes regulated by the risk SNPs were expressed in human brain and correlated with APOE expression. We conclude that these variants were most robust risk markers for AD, and their contributions to AD risk was likely to be causal. As expected, APOE and the lipoprotein metabolism pathway possess the highest weight among these contributions.

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Section: Discussionmentioning

confidence: 99%

Section: Summary Of Materials and Methods (Much Detailed In The Sumentioning

confidence: 99%

Section: Summary Of Materials and Methods (Much Detailed In The Sumentioning

confidence: 99%

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Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

et al. 2017

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“…In this study, a total of 9453 piRNAs were identified in human brains with 103 piRNAs showed altered expression in AD cases versus controls. What is more, most of the 103 piRNAs correlate with genome-wide significant risk SNPs indicating that piRNAs would be promising risk biomarkers of AD [79]. Interestingly, one research of the piRNAome on transient focal ischemia suggested that a total of 105 piRNAs showed differential expression in ischemic rat brain, although the function for the changes in those piRNA expressions still remains elusive, it was predicted that the role of altered piRNAome is to control mutagenesis through suppressing the aberrant transposon activity in the ischemic brain [80].…”

Section: Pirnas In Other Types Of Diseasesmentioning

confidence: 99%

The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

Han

2019

ExRNA

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More than a decade ago, PIWI-interacting RNA (piRNA) was discovered almost simultaneously by four different research groups. The length of this type of single stranded noncoding RNA is 24~31 nucleotides (nt), with most of the piRNAs fall into the range of 29~30 nt. PiRNAs form specific RNA-induced silencing complex with PIWI subfamily proteins, which is how piRNA got its name. PiRNAs are initially famous for the crucial roles they played in germline cells. Binding with PIWI family proteins, piRNAs is able to affect methylation of genomic DNA in germline cells and, therefore, maintaining genomic stability and suppressing transposons. Since mammalian PIWI subfamily proteins are mainly germline specific, it was once thought that piRNAs might only function in the gonadal cells. However, evidence from the later research suggest that piRNAs are broadly expressed in many kinds of somatic cells and are involved in numerous pathological condition far beyond those have been reported in the germline. For example, piRNAs were discovered to be abnormally expressed in several kinds of cancers. PiRNAs are also shown to be promising prognostic markers for various types of cancers. Interestingly, a recent research indicated that piRNAs are also regulators for pancreatic beta cell function. PiRNAs are promising regulators for the development of type 2 diabetes. From a disease-oriented point of view, this review will focus on both confirmed and proposed biological functions of piRNAs mostly in those fields beyond germline cells. Meanwhile, some of the underlying molecular mechanisms will also be mentioned.

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“…These findings also suggest that piRNAs are a shared feature of this non-aging biological system, cancers. In an earlier work, we reported associations between piRNAs and Alzheimer's disease ( 26 ), a clinical condition strongly related to aging. Cancers are just opposite to the aging diseases in renewal and proliferation capacity, which also suggests a potential role of piRNAs in cancers.…”

Section: Introductionmentioning

confidence: 97%

Transcriptome‑wide piRNA profiling in human gastric cancer

Lin

Xia

et al. 2019

Oncol Rep

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Piwi-interacting RNAs (piRNAs) comprise the largest class of non-coding RNAs. They represent a molecular feature shared by all non-aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non-tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome-wide significant and replicated cancer-risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2-fold change) expressed between the cases and controls, and 64.7% of the protein-coding genes potentially regulated by the gastric cancer-associated piRNAs were expressed in the human stomach. The expression of many cancer-associated piRNAs was correlated with the genome-wide and replicated cancer-risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.

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Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease

Cited by 79 publications

References 57 publications

Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

Genome-wide significant, replicated and functional risk variants for Alzheimer’s disease

The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

Transcriptome‑wide piRNA profiling in human gastric cancer

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