Cancer Genetics and Epigenetics 2016, Vol.4, No.1, 1-10
6
Some genes which are associated with ion channel protein gene also have relationships with the development of
Alzheimer's disease, such as, ESR2 mutations will affect the expression levels of potassium ion channel gene, and
also increases the risk of Alzheimer's disease (Pirskanen et al., 2005; Oterino et al., 2008). In the multiple-network,
ESR2 co-expressed with 25 genes include 18 coding-genes and 7 ncRNAs (Figure 6A). According to predict
ncRNA functions, we found lincRNA RP11-700H6.1 is associated with functions of ion transport and ion channel
proteins. This further demonstrates the correlation between lncRNA and ion channels.
Figure 6 Co-expression relationships of Alzheimer's disease-related genes (Blue nodes represent ion channel protein genes,
green nodes represent protein-coding genes, red nodes represent non-coding RNAs A. Co-expression of ESR2
B .Co-expression of VDAC2)
Voltage-gated anion channel VDAC2 is an Alzheimer's disease-related gene, and co-expressed with 6 ncRNAs
(Figure 6B). 5 ncRNAs enrichment to at least one GO term, and these GO term is mainly about mitochondrial
function (Figure 7B, 7C, 7D, 7E, 7F). Mitochondrial dysfunction and synaptic damage are the early phenomenon
of Alzheimer's disease (Reddy, 2013). Therefore, we speculate that 6 ncRNAs co-expressed with VDAC2 may be
involved in the pathogenesis of Alzheimer's disease.
Discussion
Probe annotation information were obtained by probe re-annotation method, and then combined with gene
expression profile datasets of Alzheimer's disease, ion channel protein gene, the correlation of gene expression
and direction consistency of co-expression in each expression profile dataset to constructed multiple-network. The
multiple-network shows ncRNAs and ion channel protein genes have regulatory relations on expression and
function, and VDAC2 and 5 ncRNAs may be involved in the pathogenesis of Alzheimer's disease.
ncRNA and ion channel protein genes, which are important biological macromolecules, involved in many
important biological processes and plays an important role in the development of many diseases. It has been found
more than ten thousand ncRNA, and the research of relationships between ncRNAs and ion channels will help us
to deepen understand the mechanisms of biological processes and diseases. However, most of the studies only
predict ncRNA functions, while ignoring the relationship between ncRNAs and ion channels (Zhao et al., 2014).
Both ncRNAs and ion channels are participated in neurodegenerative diseases and cancers. Explore relationships
between ncRNAs and ion channel protein genes will help us to better understand the pathogenesis of diseases.
Materials and methods
Probe re-annotation
Human probe sequences were obtained from Affymetrix
), Human Genome U133 Plus
2.0 Array contains 604,258 probe sequences. We obtained 99,436 human protein-coding gene transcript sequences
and 37,197 human non-coding gene transcript sequences from the Ensembl database (Flicek et al., 2011). Taking
into account the speed of update genomic data becomes faster and faster, we need to improve the accuracy of
microarray probes annotation information (Lu et al., 2007; Zhang et al., 2005). In this work, we use the probe
A
B
