Combined microRNA-141 Rescue and MAPK1 Silencing as Putative Strategy to Support Chemotherapy in Translational Stage towards Metastatic Castration-resistant Prostate Cancer – an In Vitro Model Study

Authors

  • Radostina Tsvetankova Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences
  • Ilka Tsvetkova Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences
  • Albena Apostolova Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences
  • Soren Hayrabedyan Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences
  • Krassimira Todorova Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

DOI:

https://doi.org/10.7546/CRABS.2023.08.15

Keywords:

prostate cancer, inflammation, migration, DNA methylation, NF-κB, MAPK1, microRNA-141

Abstract

Tumourigenesis is associated with disruption of cell differentiation, proliferation, migration, and abnormal DNA methylation. Deregulation of transcription factors MAPK1 and NF-κB and other post modification factors play an important role in these processes. Using AR-positive and AR-negative cell line models (LNCaP-p53+/+ and PC3-p53-/-), we found MAPK1 siRNA silencing as potentially productive approach to decrease castration-resistant cell line invasiveness, but not sufficient to abrogate anti-apoptotic, pro-inflammatory by NF-κB signalling, and so we combined this approach with miR-141 rescue (mimic) and inhibition to further modulate autophagy signalling and eventually block MAPK1/NF-κB/ROS pathways. We found miR-141 rescue to upregulate AR and NF-κB inductor ACT1 and to promote total DNA demethylation, in LNCaP, but not in PC3 cells, suggesting microRNA-141 rescue as putative enhancer to MAPK1 blockade in conjunction to pro-apoptotic chemotherapy, but only in transitional towards castration-resistance stages.

Author Biographies

Radostina Tsvetankova, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

Mailing Address:
Institute of Biology and Immunology of Reproduction,
Bulgarian Academy of Sciences
73 Tsarigradsko Shosse Blvd
1113 Sofia, Bulgaria

E-mail: r.petkova@ibir.bas.bg

Ilka Tsvetkova, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

Mailing Address:
Institute of Biology and Immunology of Reproduction,
Bulgarian Academy of Sciences
73 Tsarigradsko Shosse Blvd
1113 Sofia, Bulgaria

E-mail: i.tsvetkova@ibir.bas.bg

Albena Apostolova, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

Mailing Address:
Institute of Biology and Immunology of Reproduction,
Bulgarian Academy of Sciences
73 Tsarigradsko Shosse Blvd
1113 Sofia, Bulgaria

E-mail: albena.l.apostolova@gmail.com

Soren Hayrabedyan, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

Mailing Address:
Institute of Biology and Immunology of Reproduction,
Bulgarian Academy of Sciences
73 Tsarigradsko Shosse Blvd
1113 Sofia, Bulgaria

E-mail: shayrabedyan@ibir.bas.bg

Krassimira Todorova, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences

Mailing Address:
Institute of Biology and Immunology of Reproduction,
Bulgarian Academy of Sciences
73 Tsarigradsko Shosse Blvd
1113 Sofia, Bulgaria

E-mail: ktodorova@ibir.bas.bg

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Published

29-08-2023

How to Cite

[1]
R. Tsvetankova, I. Tsvetkova, A. Apostolova, S. Hayrabedyan, and K. Todorova, “Combined microRNA-141 Rescue and MAPK1 Silencing as Putative Strategy to Support Chemotherapy in Translational Stage towards Metastatic Castration-resistant Prostate Cancer – an In Vitro Model Study”, C. R. Acad. Bulg. Sci., vol. 76, no. 8, pp. 1286–1296, Aug. 2023.

Issue

Section

Medicine