22P - Non-Coding MIR491 is Associated with Less EGFr Expression and Greater Radiosensitivity in Human Head and Neck Cancer Cell Lines (22P)

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Basic Science
Head and Neck Cancers
Presenter James Bonner
Citation Annals of Oncology (2017) 28 (suppl_10): x1-x6. 10.1093/annonc/mdx652
Authors J.A. Bonner1, E.S. Yang2, H. Trummell2, S. Nozell2, C. Willey2, M. Bredel2
  • 1Radiation Oncology, University of Alabama at Birmingham, 35233 - Birmingham/US
  • 2Radiation Oncology, University of Alabama at Birmingham, Birmingham/US

Abstract

Background

Non-coding RNAs, such as microRNAs (miRs), are often affected by loss or amplification of adjacent tumor suppressor genes or oncogenes, respectively. MIR491 is located in close proximity to the CDKN2A locus and is frequently co-deleted with CDKN2A. MIR491 expression has correlated with inhibition of EGFr. Also, knockdown of MIR491 has been shown to increase cellular proliferation and invasion in glioma cells [Li, X et al. Oncogene, 34(13):1619-1628, 2015]. Since MIR491 deletion has been demonstrated in head and neck cancer, we sought to assess the effect of increasing MIR491 expression on EGFr expression as well as downstream signaling events and radiosensitivity.

Methods

Four human head and neck squamous cell carcinoma cells lines were studied (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R). The UM-SCC-1R and UM-SCC-6R cells were developed as cetuximab resistant cells after several months of continuous exposure to cetuximab. Previously published methods were used to transfect cells with MIR491. Also, previously described methods were used for assessments of EGFr and other downstream proteins (by immunoblot), cell proliferation, colony formation and apoptosis (annexin assay). [Bonner JA. Radiother Oncol, 92:338-344, 2009].

Results

MIR491 transfected human head and neck squamous cell carcinoma cells (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R) showed decreased expression of phosphorylated EGFr and phosphorylated AKT by immunoblot. Furthermore, these decreases in EGFr and EGFr-signaling proteins correlated with enhanced radiosensitivity as assessed by cell proliferation and colony formation. This enhanced radiosensitivity correlated with greater radiation-induced apoptosis.

Conclusions

These results suggest that MIR491 is a negative regulator of EGFr in head and neck cancer and that deletions of the non-coding MIR491 gene may be associated with radiation resistance, and may contribute to poor outcomes for certain tumors that are treated with radiotherapy. Further work will be necessary to determine if MIR491 deletions are associated with greater tumor recurrence following radiation or other DNA-damaging cancer treatments.

Clinical trial identification

N/A

Legal entity responsible for the study

James Bonner

Funding

University of Alabama Health Services Foundation

Disclosure

J.A. Bonner: Occasional consultant/honoraria for Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Serono, and Cel-Sci. E.S. Yang: Advisory Board SRATA Oncology, Research Support Eli Lilly, Novartis Research Support-AACR, Bayer C. Willey: North, Pursell & Ramos, PLC - medical-legal consultations for malpractice case review.

All other authors have declared no conflicts of interest.