Title:HOXB7 and Hsa-miR-222 as the Potential Therapeutic Candidates for Metastatic Colorectal Cancer
Volume: 11
Issue: 4
Author(s): Maryam Iman, Seyede Samaneh Mostafavi, Seyed Shahriar Arab, Sadegh Azimzadeh and Mansour Poorebrahim
Affiliation:
Keywords:
CRC, metastasis, miRNA, regulatory networks, small peptide.
Abstract: Background: Recent studies have shown that the high mortality of patients
with colorectal cancer (CRC) is related to its ability to spread the surrounding tissues,
thus there is a need for designing and developing new drugs.
Objective: Here, we proposed a combinational therapy strategy, an inhibitory peptide
in combination with miRNA targeting, for modulating CRC metastasis. In this study,
some of the recent patents were also reviewed.
Methods: After data analysis with GEO2R and gene annotation using DAVID server,
regulatory interactions of differentially expressed genes (DEGs) were obtained from
STRING, GeneMANIA, KEGG and TRED databases. In parallel, the corresponding
validated microRNAs (miRNAs) were obtained from mirDIP web server and a
miRNA-DEG regulatory network was also reconstructed. Clustering and topological analyses of the regulatory
networks were performed using Cytoscape plug-ins.
Results: We found the HOXB family as the most important functional complex in DEG-derived regulatory
network. Accordingly, an anti-HOXB7 peptide was designed based on the binding interface of its coactivator,
PBX1. Topological analysis of miRNA-DEG network indicated that hsa-miR-222 is one of the
most important oncomirs involved in regulation of DEGs activities. Thus, this miRNA, along with
HOXB7, was also considered as the potential target for inhibiting CRC metastasis. Molecular docking
studies exhibited that the designed peptide can bind to desired binding pocket of HOXB7 in a highaffinity
manner. Further confirmations were also observed in Molecular dynamics (MD) simulations carried
out by GROMACS v5.0.2 simulation package.
Conclusion: In conclusion, our findings suggest that simultaneous targeting of key regulatory genes and
miRNAs may be a useful strategy for prevention of CRC metastasis.
