Abstract
The prevalence of polycystic ovary syndrome (PCOS) has been gradually increasing among adult females worldwide. Laparoscopy drilling on ovary is the only available temporary solution with a high incidence of reoccurrence. S100A8 with S100A9 complex is believed to facilitate the cyst migration in PCOS condition. The high evident protein interaction network studies between PCOS biomarkers, cancer invasion markers, and the interactors of S100A8 confirm that this protein has strong interaction with other selective PCOS biomarkers, which may be associative in the immature cyst invasion process. Through the network studies, intensive structural and pathway analysis, S100A8 is identified as a targetable protein. In this research, the non-SELEX in silico method is adapted to construct RNA Library based on the consensus DNA sequence of Glucocorticoid Response Element (GRE) and screened the best nucleotide fragments which are bound within the active sites of the target protein. Selected sequences are joined as a single strand and screened the one which competitively binds with minimal energy. In vitro follow-up of this computational research, the designed RNA aptamer was used to infect the MCF7 cell line through Lipofectamine 2000 mediated delivery to study the anti-cell migration effect. Wound Scratch assay confirms that the synthesized 18-mer oligo has significant inhibition activity toward tumor cell migration at the cellular level.
Highlights
Nucleotide aptamers are successfully explored as better therapeutics to treat diseases and disorders
In silico non-SELEX approach is the better choice to perform the selection of aptamers, which involves the construction of an oligonucleotide library without amplification and binding them with suitable target protein unlike SELEX (Berezovski et al, 2006; Tseng et al, 2011)
We found that S100A8 directly interact with 10 proteins (Table 1)
Summary
Nucleotide aptamers are successfully explored as better therapeutics to treat diseases and disorders. Time-consuming low-throughput procedures have been in practice to design the aptamers in vitro (Ghavami et al, 2009). In silico non-SELEX approach is the better choice to perform the selection of aptamers, which involves the construction of an oligonucleotide library without amplification and binding them with suitable target protein unlike SELEX (Berezovski et al, 2006; Tseng et al, 2011). Designing the RNA aptamer for the validated biomarker helps us to normalize the disease state at the genetic level. Delivering a well-designed aptamer against response elements (REs) can control the strange translation of the target gene.
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