THESIS
2018
xv, 101 pages : illustrations ; 30 cm
Abstract
MicroRNAs (miRNAs) are evolutionarily conserved noncoding RNAs with a typical
length of 22 nucleotides. There are more than 1000 miRNA genes in the human genome
and each of them may target dozens or hundreds of different mRNAs to post-transcriptionally regulate their expression levels. Thus, it is not surprising that miRNAs
participate in numerous physiological and pathological processes. Mini-chromosome
maintenance (MCM) proteins function as essential components of pre-replicative
complex (pre-RC) in G1 phase and the helicase to unwind DNA duplex in S phase and
they are overexpressed in most cancer cells. Which miRNAs may involve in regulation
of MCM expression and DNA replication is largely unknown. Taking advantage of the
bioinformatics programs such as TargetScan and miRANda...[
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MicroRNAs (miRNAs) are evolutionarily conserved noncoding RNAs with a typical
length of 22 nucleotides. There are more than 1000 miRNA genes in the human genome
and each of them may target dozens or hundreds of different mRNAs to post-transcriptionally regulate their expression levels. Thus, it is not surprising that miRNAs
participate in numerous physiological and pathological processes. Mini-chromosome
maintenance (MCM) proteins function as essential components of pre-replicative
complex (pre-RC) in G1 phase and the helicase to unwind DNA duplex in S phase and
they are overexpressed in most cancer cells. Which miRNAs may involve in regulation
of MCM expression and DNA replication is largely unknown. Taking advantage of the
bioinformatics programs such as TargetScan and miRANda, we found that there might be
potential interaction between miRNA-214 and Mcm5/7. Real time quantitative PCR
showed that the expression of miRNA-214 was downregulated in liver cancer cell lines
HepG2 and Hep3B compared with the normal liver cell line L-02. Reintroduction of
miRNA-214 in HepG2 and Hep3B inhibited the expression of Mcm5/7 at both mRNA
level and protein level. In addition, enforced expression of miRNA-214 inhibited DNA
replication, cell cycle progression, cell proliferation and colony formation in HepG2 and
Hep3B cells. On the other hand, miRNA-214 showed much less inhibition of the
expression of Mcm5/7, cell proliferation or colony formation in LO2 cells, which may
indicate that miRNA-214 preferentially kills liver cancer cells rather than normal
counterparts. Importantly, miR-214 can also inhibit the growth of HepG2 xenografts in
nude mice. Collectively, our data suggest that miRNA-214 may regulate DNA replication
through MCM5/7 and miRNA-214 may possess preliminary drug potential against liver
cancer.
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