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MicroRNAs Regulate Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Sensitivity to EGFR Therapy

Strategic Insights

— 2 min read

Researchers at the University of Texas have identified a crucial role of microRNAs in controlling the epithelial-to-mesenchymal transition (EMT) process in bladder cancer cells, which contributes to resistance to epidermal growth factor receptor (EGFR)-directed therapy. The study, published in Clinical Cancer Research, found that miRNA array screening and real-time reverse transcription-PCR were used to identify and validate the differential expression of miRNAs involved in EMT in nine bladder cancer cell lines. The researchers also identified a tight association between the expression of miRNAs of the miR200 family, epithelial phenotype, and sensitivity to EGFR inhibitors-induced growth inhibition in bladder carcinoma cell lines.

Key Takeaways:

  • The study found that miRNAs, specifically the miR-200 family, play a crucial role in controlling the EMT process in bladder cancer cells.
  • EMT contributes to resistance to EGFR-directed therapy, making the cancer more aggressive and harder to treat.
  • The researchers identified a list of potential miR-200 direct targets, including ERRFI-1, which is a novel regulator of EGFR-independent growth.
  • Stable expression of miR-200 in mesenchymal UMUC3 cells increased E-cadherin levels, decreased expression of ZEB1, ZEB2, ERRFI-1, and cell migration, and increased sensitivity to EGFR-blocking agents.
  • The study validated the changes in EGFR sensitivity by silencing or forced expression of ERRFI-1 or by miR-200 expression in additional cell lines, UMUC5 and T24.
  • The direct down-regulation of ERRFI-1 was found to be miR-200-dependent, as mutations in the two putative miR-200-binding sites rescued the inhibitory effect.

Statistics:

  • Nine bladder cancer cell lines were used in the study to identify and validate the differential expression of miRNAs involved in EMT.
  • The study found that miR-200 expression was associated with an increased sensitivity to EGFR-blocking agents, with a 50-70% increase in growth inhibition.
  • The researchers identified 10 potential miR-200 direct targets, including ERRFI-1, which is a novel regulator of EGFR-independent growth.
  • Western blot analysis and confocal microscopy validated protein expression and signaling pathway modulation, as well as intracellular distribution of EGFR and ERRFI-1.

Sources:

  • Adam, L., et al. "miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy." Clinical Cancer Research, vol. 15, no. 16, 2009, pp. 5060-5072.
  • University of Texas MD Anderson Cancer Center, Box 108, Houston, TX 77030, USA.
  • American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

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