Publication:
Drug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer

Simple item page
dc.contributor.authorTURANLI, BESTE
dc.contributor.authorsBeklen, Hande; Gulfidan, Gizem; Arga, Kazim Yalcin; Mardinoglu, Adil; Turanli, Beste
dc.date.accessioned2022-03-14T09:24:50Z
dc.date.available2022-03-14T09:24:50Z
dc.date.issued2020-08-13
dc.description.abstractColorectal cancer (CRC) is one of the most fatal types of cancers that is seen in both men and women. CRC is the third most common type of cancer worldwide. Over the years, several drugs are developed for the treatment of CRC; however, patients with advanced CRC can be resistant to some drugs. P-glycoprotein (P-gp) (also known as Multidrug Resistance 1, MDR1) is a well-identified membrane transporter protein expressed by ABCB1 gene. The high expression of MDR1 protein found in several cancer types causes chemotherapy failure owing to efflux drug molecules out of the cancer cell, decreases the drug concentration, and causes drug resistance. As same as other cancers, drug-resistant CRC is one of the major obstacles for effective therapy and novel therapeutic strategies are urgently needed. Network-based approaches can be used to determine specific biomarkers, potential drug targets, or repurposing approved drugs in drug-resistant cancers. Drug repositioning is the approach for using existing drugs for a new therapeutic purpose; it is a highly efficient and low-cost process. To improve current understanding of the MDR-1-related drug resistance in CRC, we explored gene co-expression networks around ABCB1 gene with different network sizes (50, 100, 150, 200 edges) and repurposed candidate drugs targeting the ABCB1 gene and its co-expression network by using drug repositioning approach for the treatment of CRC. The candidate drugs were also assessed by using molecular docking for determining the potential of physical interactions between the drug and MDR1 protein as a drug target. We also evaluated these four networks whether they are diagnostic or prognostic features in CRC besides biological function determined by functional enrichment analysis. Lastly, differentially expressed genes of drug-resistant (i.e., oxaliplatin, methotrexate, SN38) HT29 cell lines were found and used for repurposing drugs with reversal gene expressions. As a result, it is shown that all networks exhibited high diagnostic and prognostic performance besides the identification of various drug candidates for drug-resistant patients with CRC. All these results can shed light on the development of effective diagnosis, prognosis, and treatment strategies for drug resistance in CRC.
dc.identifier.doi10.3389/fonc.2020.01273
dc.identifier.issn2234-943X
dc.identifier.pubmed32903699
dc.identifier.urihttps://hdl.handle.net/11424/243089
dc.identifier.wosWOS:000568518600001
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SA
dc.relation.ispartofFRONTIERS IN ONCOLOGY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcolorectal cancer
dc.subjectdrug repositioning
dc.subjectmulti-drug resistance
dc.subjectP-glycoprotein
dc.subjectco-expression networks
dc.subjectmulti-drug resistance protein
dc.subjectRESISTANCE
dc.subjectTRANSPORT
dc.subjectEXPRESSION
dc.subjectPATHWAYS
dc.subjectABCB1
dc.subjectIRINOTECAN
dc.subjectSIGNATURES
dc.subjectDISCOVERY
dc.subjectDISEASES
dc.subjectDATABASE
dc.titleDrug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer
dc.typearticle
dspace.entity.typePublication
local.avesis.ide26edd1a-14b3-4634-baaa-9fec0eb23916
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumber1273
local.journal.numberofpages13
local.journal.quartileQ2
oaire.citation.titleFRONTIERS IN ONCOLOGY
oaire.citation.volume10
relation.isAuthorOfPublication3e8c4f64-93ae-4b42-953c-35c8b07586b3
relation.isAuthorOfPublication.latestForDiscovery3e8c4f64-93ae-4b42-953c-35c8b07586b3

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Beklen et al. - 2020 - Drug Repositioning for P-Glycoprotein Mediated Co-.pdf
Size:
2.31 MB
Format:
Adobe Portable Document Format
Download

Collections

Research Outputs