Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral

Kieran Caberto Huni1, Jacky Cheung2, Madeline Sullivan2

  • 1Department of Advanced Education in Orthodontic Dentistry, School of Dental Medicine, University of Nevada-Las Vegas, 1700 W. Charleston Boulevard, Las Vegas, NV 89106, USA.

Insights

Specific microRNAs (miRNAs) correlate with oral cancer response to chemotherapy. miR-375 expression and lack of miR-27 were linked to drug resistance in oral squamous cell carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-coding microRNAs (miRNAs) are implicated in oral cancer progression and response to chemotherapy.
  • Specific miRNAs, including miR-21, miR-27, miR-145, miR-155, miR-365, miR-375, and miR-494, are potential regulators of chemotherapeutic responsiveness.

Purpose of the Study:

  • To investigate the correlation between specific miRNAs and oral cancer responsiveness to Paclitaxel, Cisplatin, and Fluorouracil (5FU).
  • To identify potential miRNA biomarkers for predicting chemotherapy outcomes in oral squamous cell carcinoma.

Main Methods:

  • Utilized commercially available oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25, CAL27) with varying chemosensitivity.
  • Assessed miRNA expression profiles (miR-375, miR-27) and correlated them with drug resistance.
  • Investigated downstream molecular targets, including Rearranged L-myc fusion (RLF), Centriolar protein B (POC1), and Nucleophosmin 1 (NPM1).

Main Results:

  • SCC9 and SCC25 cell lines exhibited the highest resistance to Paclitaxel, Cisplatin, and 5FU.
  • miR-375 expression was exclusively observed in the resistant SCC9 and SCC25 cell lines.
  • Lack of miR-27 expression was also characteristic of the resistant SCC9 and SCC25 cell lines.
  • miR-375 expression correlated with RLF upregulation and POC1 downregulation.
  • Absence of miR-27 correlated with NPM1 expression.

Conclusions:

  • Specific miRNAs, notably miR-375 and miR-27, are significantly associated with oral cancer chemoresistance.
  • These miRNAs may influence oral cancer proliferation and drug resistance through regulatory pathways involving RLF, POC1, and NPM1.
  • Further research into these miRNA-mediated mechanisms is crucial for developing novel therapeutic strategies for oral cancer.

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