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Biomarkers to target and silence stemness of breast cancer stem cell model: silencing MDR1 by siRNA

Turkish Journal of Biochemistry · Ağustos 2022

Makale Bilgileri

DergiTurkish Journal of Biochemistry
Yayın TarihiAğustos 2022
Cilt / Sayfa47 · 445-455
Erişim🔓 Açık Erişim
Özet Objectives: Aim of the study was to reveal new biomarker genes to target breast cancer stem-like cells (BCSC-like) and then sensitize BCSC-like cells to chemotherapy by silencing MDR1 gene found to be the most suitable target. Methods: Drug resistance associated genes were screened by cDNA microarray to unveil biomarker genes in drug resistance breast cancer model cells. Drug resistance was then reversed by silencing MDR1 gene in BCSC-like cells. The effect of silencing was monitored by real-time cell proliferation analysis. Differential expressions of MDR1, ALDH1A3, EGFR and BAG4 genes were identified by real-time PCR. P-glycoprotein (P-gp) expression level and its activity were investigated by Western blot and flow cytometry measurements, respectively. Results: 16 new biomarker genes were identified upon gene expression analysis by cDNA microarray. MDR1 gene was selected as the most potent target gene and silencing of it caused down-regulation of MDR1, ALDH1A3, EGFR, BAG4 expression and P-glycoprotein activity and expression in BCSC-like cells. At the end, silenced BCSC-like cells were found to be more responsive to paclitaxel therapy. Conclusions: In conclusion, siMDR1 silencing is an effective way to reverse multidrug resistance and malignancy. New biomarker genes revealed in this study require to be investigated to target stemness of BC.

Yazarlar (4)

1
Gamze Yıldırım
ORCID: 0000-0002-6764-7349
2
Meltem Demirel Kars
3
Gökhan Kars
ORCID: 0000-0002-2507-2305
4
Hamdi Şükür Kılıç

Anahtar Kelimeler

ALDH1A3 breast cancer stem cells EGFR microarray paclitaxel siMDR1

Kurumlar

Necmettin Erbakan Üniversitesi
Meram Turkey
Selçuk Üniversitesi
Selçuklu Turkey

Metrikler

1
Atıf
4
Yazar
6
Anahtar Kelime