Expression of miRNA in 5-FU resistant esophageal cancer

Prasit Mahawongkajit1, Prakitpunthu Tomtitchong1

  • 1Department of Surgery, Faculty of Medicine, Thammasat University, Amphur Klongluang, Pathumthani 12120, Thailand.

Insights

Drug resistance to fluoropyrimidine plus platinum chemotherapy in esophageal squamous cell carcinoma (ESCC) is a challenge. This study identified specific microRNAs (miRNAs) differentially expressed in 5-FU resistant ESCC cells, offering potential targets for overcoming resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Esophageal squamous cell carcinoma (ESCC) treatment commonly involves fluoropyrimidine plus platinum (FP) chemotherapy.
  • Acquired drug resistance to chemotherapy, particularly 5-fluorouracil (5-FU), remains a significant obstacle in ESCC treatment.
  • MicroRNAs (miRNAs) are recognized as key regulators in various human cancers and play roles in drug resistance.

Purpose of the Study:

  • To investigate the differential expression profile of miRNAs in ESCC.
  • To identify specific miRNAs associated with 5-FU resistance in ESCC cell lines.
  • To establish a 5-FU resistant (5-FUR) ESCC cell line model for miRNA expression analysis.

Main Methods:

  • Development of 5-FU resistant (5-FUR) ESCC cell lines (TE10-5-FUR and TE11-5-FUR) from parental cell lines (TE10 and TE11).
  • High-throughput sequencing or microarray analysis to profile miRNA expression in parental and 5-FUR cell lines.
  • Comparative analysis to identify differentially expressed miRNAs between sensitive and resistant cells.

Main Results:

  • In TE10-5-FUR cells compared to TE10, 50 miRNAs were upregulated and 119 were downregulated.
  • In TE11-5-FUR cells compared to TE11, 140 miRNAs were upregulated and 12 were downregulated.
  • Two common upregulated miRNAs (miR-146a, miR-483-5p) and five common downregulated miRNAs (miR-34a, miR-141, miR-200b, miR-200c, miR-205) were identified in both resistant cell lines.

Conclusions:

  • The study successfully established 5-FU resistant ESCC cell models.
  • Specific miRNA expression profiles are associated with 5-FU resistance in ESCC.
  • The identified candidate miRNAs warrant further investigation for their functional roles in ESCC chemoresistance and potential therapeutic targeting.