Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

Abstract

Head and neck cancers (HNCs) rank as the sixth common and the seventh leading cause of cancer-related death worldwide, with an estimated incidence of 600,000 cases and 40–50% mortality rate every year. Radiotherapy is a common local therapeutic modality for HNC mainly through the function of ionizing radiation, with approximately 60% of patients treated with radiotherapy or chemoradiotherapy. Although radiotherapy is more advanced and widely used in clinical practice, the 5-year overall survival rates of locally advanced HNCs are still less than 40%. HNC cell resistance to radiotherapy remains one of the major challenges to improve the overall survival in HNC patients. Non-coding RNAs (ncRNAs) are newly discovered functional small RNA molecules that are different from messenger RNAs, which can be translated into a protein. Many previous studies have reported the dysregulation and function of ncRNAs in HNC. Importantly, researchers reported that several ncRNAs were also dysregulated in radiotherapy-sensitive or radiotherapy-resistant HNC tissues compared with the normal cancer tissues. They found that ectopically elevating or knocking down expression of some ncRNAs could significantly influence the response of HNC cancer cells to radiotherapy, indicating that ncRNAs could regulate the sensitivity of cancer cells to radiotherapy. The implying mechanism for ncRNAs in regulating radiotherapy sensitivity may be due to its roles on affecting DNA damage sensation, inducing cell cycle arrest, regulating DNA damage repair, modulating cell apoptosis, etc. Additionally, clinical studies reported that in situ ncRNA expression in HNC tissues may predict the response of radiotherapy, and circulating ncRNA from body liquid serves as minimally invasive therapy-responsive and prognostic biomarkers in HNC. In this review, we aimed to summarize the current function and mechanism of ncRNAs in regulating the sensitivity of HNC cancer cells to radiotherapy and comprehensively described the state of the art on the role of ncRNAs in the prognosis prediction, therapy monitoring, and prediction of response to radiotherapy in HNC.

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

“…Recently, lncRNAs have gained increasing attention in targeted therapy of human cancer ( 38 – 40 ). At present, targeting lncRNAs can be achieved through multiple different approaches, such as transcription block, degradation and gene-editing technology ( 41 , 42 ).…”

Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression

“…ncRNAs, a special class of RNA transcripts, do not encode proteins but exhibit high specificity and stability, making them crucial for assessing the occurrence and progression of cancer [ 23 , 24 ]. Based on their functions, ncRNAs are typically categorized into housekeeping RNAs and regulatory RNAs [ 25 ]. Regulatory RNAs mainly include miRNAs, lncRNAs, and circRNAs [ 23 , 24 , 25 , 26 ].…”

“…Based on their functions, ncRNAs are typically categorized into housekeeping RNAs and regulatory RNAs [ 25 ]. Regulatory RNAs mainly include miRNAs, lncRNAs, and circRNAs [ 23 , 24 , 25 , 26 ]. miRNAs are extensively studied small non-coding RNAs (sncRNAs) in eukaryotes and consist of approximately 22 nucleotides (nt) in length [ 27 ].…”

Association between single nucleotide polymorphisms in DNA repair genes and the efficacy of radiotherapy in nasopharyngeal carcinoma patients

“…Worldwide, the deep anatomic localization of NPC and its late diagnosis limit therapeutic approaches, and radiotherapy is still the main and the most effective treatment of NPC [3]. Scientific evidence has shown that radiotherapy destroys tumour cells by acting directly on the DNA (direct effect), and indirectly by free radicals generated by ionization leading to DNA base lesion (indirect effect) [4]. This DNA injury eventually impacts cell proliferation and changes the cell cycle, inducing cellular apoptosis or activating death pathways [5].…”