TITLE:
An Integrated Analysis Method for miRNA, lncRNA and mRNA Profiles Based on Their Functional and Positional Relationships
AUTHORS:
Li Guo, Sheng Yang, Yang Zhao, Hui Zhang, Qian Wu, Feng Chen
KEYWORDS:
ncRNA; mRNA; Profile; Integrative Analysis
JOURNAL NAME:
Engineering,
Vol.5 No.10B,
October
23,
2013
ABSTRACT: ncRNAs have been identified as potential regulatory
molecules and have multiple biological roles. Aberrant expression of specific
ncRNAs contributes to multiple biological processes and many human diseases.
Herein, we simultaneously profiled miRNA, lncRNA and mRNA in human HepG2 and
L02 cells applying high-throughput sequencing and micro-array
technologies. Abnormal miRNA, lncRNA and mRNA profiles were assessed through
fold change filtering. A cross-platform integrated analysis method was
developed to analyze differentially expressed miRNA, lncRNA and mRNA profiles.
miRNA-mRNA interaction was analyzed according to their functional relationships.
Target mRNAs of aberrantly expressed miRNAs were obtained from experimentally
validated datasets or predicted using some programs. Generally, multiple target
mRNAs were involved, and they have versatile roles by functional enrichment
analysis. Ac-cording to actual expression datasets in the study, compared to
deregulated miRNAs, these theoretical target mRNAs showed various expression
patterns. The consistent or inconsistent expression was mainly derived from
complex, mul-tiple, flexible and alternative regulatory relationships between
miRNA and mRNA. Further, miRNA/mRNA and lncRNA were completely surveyed based
on their location distributions on human chromosomes. Many miRNA-lncRNA
and mRNA-lncRNA pairs always were located on the same strand or different
strands in the specific genomic region. Due to the location distributions, they
might have partly or completely overlapped regions or they could be
reverse complementarily binding. These miRNA/mRNA-lncRNA pairs showed consistent or
inconsistent expression pat-terns, although they might have functional
relationships through reverse complementarily binding events. Moreover, we also
detected and analyzed various isomiRs from a given miRNA locus, including those
isomiRs with 3’ additional
non-template nucleotides. These isomiRs, especially for those 5’ isomiRs with the new “seed sequences”
through “seed shifting” events, maybe have potential biological roles as well
as isomiR repertoire and their expression patterns. The integrative analysis
provides potential functional relationships between miRNA, lncRNA and mRNA
across different datasets. The complex and various expression patterns suggest
a robust regulatory network across different regulatory molecules and their
targets.