PLK1 Mitigates Intervertebral Disc Degeneration by Delaying Senescence of Nucleus Pulposus Cells.

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain; however, the molecular mechanisms involved in the pathogenesis of IVDD are not fully understood. Polo-like kinase 1 (PLK1) plays numerous roles in the cell cycle, including in cell proliferation and senescence. To investigate the involvement of PLK1 in IVDD, we used patient tissues and an animal model of IVDD. Samples were analyzed via immunoblotting, quantitative real-time polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry. Our results demonstrated that PLK1 expression was decreased in nucleus pulposus cells (NPCs) of degenerative IVDs. The inhibition of PLK1 kinase activity in normal NPCs increased the expression of p53 protein, inhibited cell proliferation, and induced senescence. Our results suggest that PLK1 regulates the degeneration of the IVD through p53, revealing the function and mechanism of PLK1 in IVDD and providing a theoretical basis and experimental evidence for the potential treatment of low back pain.

Prognostic values of m6A RNA methylation regulators in differentiated Thyroid Carcinoma.

N6-methyladenosine (m6A) is the most prevalent modification of RNA in mammals. m6A RNA methylation levels are dynamically regulated by m6A RNA methylation regulators. While increasing evidence has suggested that m6A RNA methylation is vital in the initiation and progression of human carcinoma, little is known about the expression and effect of m6A RNA methylation regulators in differentiated thyroid carcinoma (DTC). Herein, we demonstrate that most of the thirteen main m6A RNA methylation regulators are differentially expressed in DTC tissues and normal thyroid tissues. Based on consensus clustering of m6A RNA methylation regulators, DTC cases were divided into two subgroups (TC1 and TC2). Compared with the TC1 subgroup, the TC2 subgroup was associated with a poorer prognosis, older age, higher T grade, higher N grade and higher TNM stage. The results indicated that alteration of m6A RNA methylation regulators was closely related to DTC. We further established a risk signature of four m6A RNA methylation regulators that could evaluate prognosis and clinicopathological features in DTC. Finally, the results of the TCGA analysis were verified by other cohorts from Gene Expression Omnibus (GEO) database. In conclusion, m6A RNA methylation regulators play a crucial part in the progression of DTC and are potentially useful for evaluating the prognosis and providing potential novel insights into treatment strategies.

Low expression of ryanodine receptor 2 is associated with poor prognosis in thyroid carcinoma.

Genetic alterations are vital in the progression of thyroid carcinoma. Ryanodine receptor 2 (RyR2) is reported to serve an important role in several types of human carcinoma. However, the expression and effect of RyR2 in thyroid carcinoma remain unknown. Therefore, the present study analyzed the status of RyR2 in thyroid carcinoma using bioinformatics tools. The mRNA profiles of thyroid carcinoma were downloaded from The Cancer Genome Atlas. RyR2 was distinguished as a differentially expressed gene that has not been reported in thyroid carcinoma. Further analysis indicated that there was selective downregulation of RyR2 expression in thyroid carcinoma tissues compared with that in normal thyroid tissues. Survival analysis showed that RyR2 expression was associated with poorer disease-free survival (DFS) for all patients with thyroid carcinoma. Univariate analysis revealed that a low expression of RyR2 was significantly associated with lymphatic metastasis, extracapsular extension, and the Tumor-Node-Metastasis stage. Cox analysis demonstrated that RyR2 was an independent prognostic factor in thyroid carcinoma for DFS. The biological processes and signaling pathways of RyR2 were reviewed with Gene Set Enrichment Analysis. In conclusion, the present study has revealed that RyR2 is downregulated in thyroid carcinoma, and that low expression of RyR2 is associated with poor prognosis in patients with thyroid carcinoma. RyR2 may therefore serve as a promising tumor suppressor gene in thyroid carcinoma.

Evaluation of neutrophil-to-lymphocyte ratio and calcitonin concentration for predicting lymph node metastasis and distant metastasis in patients with medullary thyroid cancer.

The aim of the present study was to investigate potential predictive factors of lymph node metastasis (LNM) and distant metastasis (DM) of medullary thyroid cancer (MTC). A total of 61 patients newly diagnosed with MTC at the General Hospital of the Chinese People's Liberation Army between January 2001 and January 2016 were enrolled and divided into two groups according to the results of preoperative examinations and surgical histopathology as follows: Group NM (without metastases), and group M (with metastases). Univariate logistic regression analysis demonstrated that sex, tumor size, preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR), and concentration of carcinoembryonic antigen (CEA) and calcitonin (Ctn), were significantly associated with LNM and DM. The multivariate analysis revealed that a Ctn concentration of >500 pg/ml [odds ratio (OR)=21.422; 95% confidence interval (CI): 2.611-175.731] and the NLR (OR=5.918; 95% CI: 1.147-30.541) were positively correlated with LNM and DM. The optimal cut-off value of the NLR for predicting LNM and DM obtained from receiver operating characteristic curve analysis was 1.784 (sensitivity 68.3% and specificity 80%), and the area under the curve was 0.717. In conclusion, the findings of the present study strongly suggest that inflammation and immune activation of MTC cells promote LNM and DM, and that higher values of NLR and Ctn concentration confer a high risk of metastasis.