MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

Abstract

Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

Figure 1

MiRNAs involved in radioresistance of head and neck cancer. This figure shows a regulation of key processes involved in head and neck cancers radioresistance through miRNAs and their targets. ANXA1: Annexin 1, BCL2: B-cell CLL/Lymphoma 2, ATM: Ataxia Telangiectasia Mutated, MCL1: Myeloid cell Leukemia 1, CD40LG: CD40 Ligand, MYB v-Myb: avian myeloblastosis viral oncogene homolog, SMC1A: Structural Maintenance of Chromosomal 1 A, CDH 1: Cadherin 1, PTEN: Phosphatase and Tensin homolog, XIAP: X-linked Inhibitor of Apoptosis E3 ubiquitin Protein, WNT2B: wingless-type MMTV integration site family member 2B, RAB14: member of RAS oncogene family, HIF-1α: hypoxia-inducible factor 1 alpha subunit, TGF-WNT: transforming growth factor-wingless-type MMTV integration site family, RECK: reversion-inducing cysteine rich protein with Kazal motifs, MDR1: Multi-Drug Resistance gene 1, IL8: Interleukin 8, HSP90AA1: Heat Shock protein 90 kDa Alpha (cytosolic) Class A Member 1, ICAM 1: Intercellular Adhesion Molecule 1, Myc v-Myc: Avian Myelocytomatosis viral oncogene homolog, ICAM 2: Intercellular Adhesion Molecule 2, CTNNB1: Catenin (Cadherin associated protein) Beta1, LEF1: Lymphoid Enhancer-Binding Factor 1, CDK1: Cyclin-Dependent Kinase 1, CXCR4: Chemokine (c-x-c motif) Receptor 4, WNT1: wingless-type MMTV integration site family member 1, TWIST1: Twist Basic Helix-Loop-Helix Transcription Factor 1.