MiR-548 K regulatory effect on the ABCG2 gene expression in MDR breast cancer cells

Cancer Rep (Hoboken). 2023 Jun;6(6):e1816. doi: 10.1002/cnr2.1816. Epub 2023 May 11.

Abstract

Background: multidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such as ABCG2 (BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition.

Aims: In the present study, we used bioinformatics and experimental analysis to investigate the role of miR-548 K, in the modulating of ABCG2, in MDR breast cancer cells.

Methods and results: In silico inspections introduce 14 microRNAs targeting 3'-UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR-548 k with ABC transporter family. The expression level of ABCG2 gene in MCF7-MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR-548 K in MCF7-MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in the ABCG2 transcripts level. Additional studies on patient samples revealed that the expression of ABCG2 showed an increase in ABCG2 level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre-operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR-548 K in NCDR patients was revealed.

Conclusion: The results of our study suggest that miR-548 K may be involved in modulating the expression of ABCG2 in MDR breast cancer cells.

Keywords: ABCG2; breast cancer; miR-548 k; multi drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / pharmacology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Cell Line, Tumor
  • Drug Resistance, Multiple / genetics
  • Female
  • Gene Expression
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • MicroRNAs
  • ATP-Binding Cassette Transporters
  • ABCG2 protein, human
  • MIRN548 microRNA, human