Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia
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Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated how OCT4-PG1 pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivity to chemotherapy were evaluated after OCT4-PG1 silencing. Besides we set up a STRING network. Results showed that after OCT4-PG1 silencing, cells expressed OCT-4 gene and protein to a lesser extent than mock cells. The gene and protein expression of ABCB1, as well as its activity were reduced. On the other hand, ALOX5 and ABCC1 genes was increased even as the activity of this transporter. Moreover, the silencing cells become sensitive to two chemotherapics tested. The network structure demonstrated that OCT4-PG1 protein interacts directly with OCT-4, SOX2, and NANOG and indirectly with ABC transporters. We conclude that OCT4-PG1 pseudogene plays a key role in the regulation OCT-4 transcription factor, which alters MDR phenotype in the FEPS cell line.
KeywordsABC transporters Cancer stem cells MRP1 protein P-glycoprotein STRING database
Carboxy fluorescein diacetate
Cancer stem cells
Human embryonic stem cells
Multidrug resistance associated protein
- Rho 123
The authors thank Dr. Vivian Rumjanek (Tumoral Immunology Laboratory at the Medical Biochemistry Institute of the Federal University of Rio de Janeiro, Brazil) for providing and allowing the use of the FEPS cell line.
This work was supported by the National Program for Academic Cooperation (PROCAD/CAPES) [Grant Numbers 2951/2014], Brazil. Lettnin, A.P. received a graduate fellowship from CAPES. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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