ABSTRACT
Nasopharyngeal carcinoma (NPC) originates from the nasopharyngeal epithelium. hsa_circ_0135761 (circEFR3A), a newly identified circRNA, presented elevation in NPC via high-throughput sequencing. This study aimed to clarify the molecular mechanism of circEFR3A in the carcinogenesis of NPC. Based on RT-qPCR, subcellular fractionation, RNase R digestion and actinomycin D assays, we evaluated circEFR3A expression characteristics in NPC cells. We found that the circEFR3A was located in the cytoplasm of NPC cells, presented upregulation and stably expressed in NPC cells. Loss-of-function assays clarified the effects of circEFR3A on NPC cell malignant behaviors. The results demonstrated that circEFR3A knockdown facilitated NPC cell apoptosis but repressed NPC cell proliferation and migration. Furthermore, the regulatory mechanism of circEFR3A in NPC was explored. Bioinformatics and mechanism experiments revealed that cicrEFR3A positively modulated EFR3A by competitively binding with miR-654-3p in NPC cells. Additionally, rescue assays showed that the suppressive effects of cicrEFR3A knockdown on NPC cell proliferation, migration and apoptosis were countervailed by EFR3A upregulation. Xenograft tumor-bearing mouse models were established to investigate the role of cicrEFR3A in NPC tumorigenesis in vivo, and the results indicated that circEFR3A silencing suppressed tumor growth in mice. In conclusion, circEFR3A is highly expressed and functions as an oncogene in NPC progression. circEFR3A facilitates NPC cell proliferation and migration by binding to miR-654-3p to upregulate EFR3A, providing a potential new direction for seeking therapeutic plans for NPC.
Subject(s)
MicroRNAs , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , RNA, Circular , Animals , Humans , Mice , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , RNA, Circular/geneticsABSTRACT
BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.
