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MiR-135b-5p promotes cetuximab resistance in colorectal cancer by regulating FOXN3

Chun Peng1, Xiaoqing Li1, Yuhui Yao1

  • 1Department of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Cancer Biology & Therapy
|July 5, 2024
PubMed

Insights

MicroRNA-135b-5p (miR-135b-5p) promotes colorectal cancer (CRC) resistance to cetuximab by regulating EMT and Wnt/β-catenin signaling. Suppressing miR-135b-5p enhances CRC sensitivity to cetuximab.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) treatment faces challenges due to primary and acquired resistance to targeted therapies.
  • MicroRNA (miRNA) dysregulation is implicated in CRC development, with miR-135b-5p showing aberrant expression in CRC tissues.
  • The specific role of miR-135b-5p in cetuximab (CTx) resistance in CRC remains unclear.

Purpose of the Study:

  • To investigate the correlation between miR-135b-5p expression and cetuximab resistance in colorectal cancer.
  • To elucidate the underlying molecular mechanisms by which miR-135b-5p influences CRC cell behavior and drug resistance.

Main Methods:

  • Analysis of miR-135b-5p expression using the GEO database and RT-qPCR in CRC cell lines.
  • Assessment of cell proliferation, viability, migration, and invasion using CCK-8, colony formation, wound-healing, and transwell assays.
  • Investigation of target protein interactions via Western blot, focusing on the epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathways.

Main Results:

  • Suppression of miR-135b-5p significantly increased cetuximab sensitivity in resistant CRC cells, reducing proliferation, migration, and invasion.
  • miR-135b-5p was found to regulate the EMT process and Wnt/β-catenin signaling pathway by downregulating FOXN3.
  • Knockdown of miR-135b-5p led to increased FOXN3 expression, promoting EMT and activating the Wnt/β-catenin pathway, thereby enhancing CTx resistance.

Conclusions:

  • miR-135b-5p plays a crucial role in mediating cetuximab resistance in colorectal cancer.
  • Targeting miR-135b-5p presents a potential therapeutic strategy to overcome cetuximab resistance in CRC.
  • The findings highlight the regulatory role of miR-135b-5p in EMT and Wnt/β-catenin signaling in the context of CRC drug resistance.
Keywords:
Colorectal cancerFOXN3cetuximabmiR-135b-5ptumor resistance

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