lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world. To improve the quality of diagnostics and patients’ treatment, new and effective biomarkers are needed. Recent studies have shown that the expression level of different types of long non-coding RNAs (lncRNAs) is dysregulated in HNSCC and correlates with many biological processes. In this study, the response of lncRNAs in HNSCC cell lines after exposure to irradiation and cytotoxic drugs was examined. The SCC-040, SCC-25, FaDu, and Cal27 cell lines were treated with different radiation doses as well as exposed to cisplatin and doxorubicin. The expression changes of lncRNAs after exposure to these agents were checked by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target prediction was performed using available online tools and classified into specific biological processes and cellular pathways. The results indicated that the irradiation, as well as chemoexposure, causes changes in lncRNA expression and the effect depends on the cell line, type of agents as well as their dose. After irradiation using the dose of 5 Gy significant dysregulation of 4 lncRNAs, 10 Gy-5 lncRNAs, and 20 Gy-3 lncRNAs, respectively, were observed in all cell lines. Only lncRNAs Zfhx2as was down-regulated in all cell lines independently of the dose used. After cisplatin exposure, 14 lncRNAs showed lower and only two higher expressions. Doxorubicin resulted in lower expressions of eight and increased four of lncRNAs. Common effects of cytotoxic drugs were observed in the case of antiPEG11, BACE1AS, PCGEM1, and ST7OT. Analysis of the predicted targets for dysregulated lncRNAs indicated that they are involved in important biological processes, regulating cellular pathways connected with direct response to irradiation or chemoexposure, cellular phenotype, cancer initiating cells, and angiogenesis. Both irradiation and chemoexposure caused specific changes in lncRNAs expression. However, the common effect is potentially important for cellular response to the stress and survival. Further study will show if lncRNAs are useful tools in patients’ treatment monitoring.

PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

“…Thus, they could assist in identifying various pathologies such as cancer. Additionally, they could also potentially provide information on prognosis or responsiveness to chemo- and radiotherapy [ 12 , 16 , 17 , 18 ].…”

YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

“…It occurs in the epithelial tissues of the aerodigestive tract [1]. Tumours may be divided according to their localization: tongue, oral, laryngeal, or nasopharyngeal squamous cell carcinomas (TSCC, OSCC, LSCC, and NSCC, respectively) [2]. Tobacco smoking, alcohol consumption, and human papilloma virus (HPV) infections are the most common risk factors.…”

“…Changes in these genes result in the loss of their functions and the development of disease [4]. Commonly used therapies involve surgical resection, radiotherapy, chemotherapy, or a combination of these [1][2][3][4]. Unfortunately, owing to high resistance to radio and chemotherapy, as well as a high capacity for both local and remote metastasis, standard treatments are often ineffective, leading to high mortality rates among HNSCC patients [2].…”

“…Commonly used therapies involve surgical resection, radiotherapy, chemotherapy, or a combination of these [1][2][3][4]. Unfortunately, owing to high resistance to radio and chemotherapy, as well as a high capacity for both local and remote metastasis, standard treatments are often ineffective, leading to high mortality rates among HNSCC patients [2]. It is crucial to find new approaches in personalized medicine for the treatment of HNSCC, and knowledge of molecular biology may be of help in developing these new therapies.…”

“…Analysis of protein-coding genes (sequence changes) and their transcripts (alternative splicing forms, RNA editing) has not led to spectacular improvements in HNSCC treatment and outcome [1][2][3]. Because of this lack of progress, the search for new treatment strategies and biomarkers in oncology now focusses on the analysis and usage of non-coding RNAs (ncRNAs) [1][2][3]. Most of the human genome, about 98%, consists of ncRNAs [1][2][3][4][5][6][7], and they have important roles in many cellular processes [1][2][3][4][5][6][7].…”