| Summary: | 碩士 === 國立清華大學 === 電機工程學系 === 104 === Background
Discovery of induced pluripotent stem cells (iPSCs) has shed light on the potential of regenerative medicine, but some evidences reveal iPSCs are similar to oncogenic foci (OF), a form of in vitro produced tumor cells. These evidences indicate that stem cells and cancer cells have intensive relation. Also, recent studies exhibit that the cell cycle play a central roles in development and carcinogenesis. Thus, how to unravel the mechanism of cell cycle progression in stem and cancer cells through genetic-and-epigenetic regulations using big databases is a big issue.
Results
The real genetic-and-epigenetic cell cycle networks (GECCNs) of stem cells (embryonic stem cells, ESCs) and cancer cells (HeLa cells) are constructed by applying the system modeling, system identification and big database mining. For convenience of analysis, the real GECCNs are reduced into the core GECCNs of HeLa cells and ESCs by applying principal network projection (PNP). In this study, we investigated carcinogenic mechanisms during cell cycle progression by using common core GECCNs between HeLa cells and ESCs to clarify the potential carcinogenic mechanisms of iPSCs (ESC-like cells). Furthermore, we investigated cervical carcinogenic mechanisms by applying the big mechanism analysis of the specific core GECCN in HeLa cells. By integrating information of drug databases, the result in the specific core GECCNs of HeLa cells could provide the multiple drug for cervical cancer treatment with minimal side effects on the other genes in the core GECCN of ESCs and HeLa cells.
Conclusions
The results indicated that the iPSC induction factors, LIN28 and OCT4, dysregulating LET7B and HIF1A, respectively, results in the carcinogenic risk of iPSCs. Additionally, the accumulated genetic mutations and DNA methylation, and dysregulations of MIR29C, MIR34A, MIR98, MIR215 and MIR935 during the G1, S, and G2 phases resulted in aberrant cell proliferation which also resulted from dysregulations of MIR17 during the M phases. Dysregulation of MIR192 led to metastatic cervical cancer during the G1 and G2 phases. Moreover, the accumulated genetic mutations and DNA methylation during the S and G2 phases, dysregulations of MIR34A during the S phases and dysregulations of MIR192 during the G2 phases could trigger ineffectively DNA repair, which could induce apoptosis. Thus, the accumulated genetic mutations and DNA methylation during the G2 and S phases and dysregulation of MIR192 during the G2 phase gave rise anti-apoptosis of cervical cancer cells to prevent the decrease of genetic mutation. We finally proposed the multiple drug, including METHOTREXATE, QUERCETIN and MIMOSINE that affect ARID5B, STK17B and CCL2, respectively, for the treatment of cervical cancer.
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