- Introduction to Cancer Systems Biology 7
target.8,13Additionally, using homology modeling and docking simulation,
aurovertin B and citreoviridin were screened out to inhibit ATP synthase
and found to trigger cancer cell death. We proved that citreoviridin-
induced response network was involved in protein folding by proteomics and
phosphoproteomics5,13Furthermore, targeting both ectopic ATP synthase
and 26s proteasome induces ER stress in breast cancer cells.^20 In vivostudy
showed that citreoviridin induces alterations in the expression of glucose
metabolism-related enzymes in lung cancer.^21
The tripeptide sequence RGD (Arg-Gly-Asp) is a common cell recog-
nition motif, which is a part of integrin-binding ligands.^22 We synthesized
a cyclic RGD (Tpa-RGDWPC, cRGD) with rigid skeleton that can bind
closely to its acceptor and further measured the expression profile of cRGD-
treated MCF-7 cells with time-course proteomics, and finally used clustering
analysis to reveal the temporal patterns of altered protein expression that
can be classified as early, intermediate, and late response proteins.^22 These
results demonstrate a molecular explanation for the properties of cRGD
in cancer cells and provide valuable insight towards their role in cancer
therapy.^22
In addition to the study of molecular regulations of drugs, proteomics
can also help to study the molecular mechanism of non-coding RNA such
as microRNAs (miRNAs). MiRNAs are a class of small, endogenous, and
highly conserved non-coding RNAs that are found abundantly in eukaryotic
cells.^23 In our previous study, we combined a quantitative proteomics
and stable isotope labeling to identify the global profile of miR-148a-
regulated downstream proteins which were involved in neural development.
Further validation by silencing of miR-148a in zebrafish found the abnormal
morphology and decreased expression of neuron-related markers in the
developing brain.^24 This convincing example shows that proteomics can
facilitate the discovery of novel functions in non-coding RNAs.
Integrating transcriptomics and proteomics is useful in revealing drug
response mechanisms. For example, tanshinone IIA (TIIA) is a diterpene
quinone extracted from the plant Danshen (Salvia miltiorrhiza), which is
used in traditional Chinese medicine.11,25 By analyzing RNA-sequencing
and proteome data in TIIA-treated gastric cancer cells, TIIA was found
to suppress cell growth by blocking glucose metabolism.^11
- Conclusion
Systems biology requires omics techniques which generate high-throughput
data and enable a holistic view of gene or protein expression related to