THESIS
2018
xii, 118 pages : illustrations (some color) ; 30 cm
Abstract
DNA replication initiation is a tightly controlled process in normal cells to ensure the faithfulness
and accuracy of DNA replication. In contrast, aberrant expression of DNA replication-initiation
proteins results in deregulated cell proliferation in cancer cells. However, the mechanisms that
modulate expression of DNA replication-initiation proteins in normal and cancer cells are still
largely unclear. miRNAs, most of which are downregulated in cancer, might be one of possible
mechanisms that regulate DNA replication-initiation proteins. In this study, we demonstrate that
miR-495-3p and miR-370-3p repress DNA replication licensing, cell proliferation in vitro and in
vivo by targeting MCM2. Besides, clinical evidence shows that expressions of miR-495-3p and
miR-370-3p are signi...[
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DNA replication initiation is a tightly controlled process in normal cells to ensure the faithfulness
and accuracy of DNA replication. In contrast, aberrant expression of DNA replication-initiation
proteins results in deregulated cell proliferation in cancer cells. However, the mechanisms that
modulate expression of DNA replication-initiation proteins in normal and cancer cells are still
largely unclear. miRNAs, most of which are downregulated in cancer, might be one of possible
mechanisms that regulate DNA replication-initiation proteins. In this study, we demonstrate that
miR-495-3p and miR-370-3p repress DNA replication licensing, cell proliferation in vitro and in
vivo by targeting MCM2. Besides, clinical evidence shows that expressions of miR-495-3p and
miR-370-3p are significantly decreased, while MCM2 is upregulated in human stomach cancer
tissues compared with the adjacent normal tissues. These data suggest that miR-495-3p and miR-370-3p function as tumor suppressors by targeting MCM2 in cancer, and these findings may
provide clues for cancer detection and therapy.
Lung cancer is a deadly disease due to metastasis in late stages. To investigate the mechanisms of
metastasis in lung cancer, we identified a CEP72 mutation in lung cancer metastatic lymph nodes
by whole exosome sequencing. We found that CEP72 is needed for mitosis, migration and invasion
of lung cancer cells. Importantly, cell polarity and branched F-actin formation are impaired in
CEP72-depleted cells, suggesting that CEP72 is involved in the migration and invasion of lung
cancer cells by promoting F-actin formation.
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