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.
| Date of Award | 2018 |
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| Original language | English |
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| Awarding Institution | - The Hong Kong University of Science and Technology
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Studies of MiRNA-214 as a regulator of DNA replication initiation proteins and a potential anticancer agent
WANG, J. (Author). 2018
Student thesis: Doctoral thesis