Protein Network Studies on PCOS Biomarkers With S100A8, Druggability Assessment, and RNA Aptamer Designing to Control Its Cyst Migration Effect

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.

Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome

“…In addition to infertility, PCOS can give rise to hyperandrogenism, oligomenorrhea, hyperinsulinemia, chronic anovulation, and an increased risk of metabolic disorders such as type 2 diabetes and cardiovascular disease ( Louwers and Laven, 2020 ; Osibogun et al, 2020 ). Critically, there has been a steady rise in the prevalence of PCOS worldwide among adult women ( Manibalan et al, 2020 ). This has contributed to a need for further investigation of the mechanisms behind PCOS and for the development of efficient treatment strategies.…”

Discovering common pathogenetic processes between SARS-CoV-2 infection and polycystic ovary syndrome based on an integrated bioinformatics approach and experiment validation

“…According to our ndings in the PPI network, TLR2 interacted with MYD88, TLR1, IRF3, and other key players in the in ammatory response signaling pathway 41,42 . S100A9 could potentially interact with S100A8, and its complex was believed to facilitate cyst migration in PCOS development 43 . S100A9 could increase the production of in ammatory cytokines and disturb the steroidogenesis of PCOS 44 .…”

Amplification of an Electrochemiluminescence-Emissive Aptamer into DNA Nanotags for Sensitive Fecal Calprotectin Determination

“…Getting down to the association with calprotectin (Cal. ), even though the handpicked AptA8 in Table S1 had been registered as the best (K D = 2.90 × 10 −8 M) in the database (also in Figure 2D-a), 46 it does not guarantee bioequivalency in the context of holoproteins for the epitope perhaps resides deeply in between S100A8 (S100 Ca 2+ -binding protein A8, ∼8 kDa) and A9 (∼14 kDa) the heterodimer. 47 Such an unknown steric hindrance would result in failures in the event of Cal.…”