Identification of m6A-related lncRNAs-based signature for predicting the prognosis of patients with skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the fastest developing malignancies with strong aggressive ability and no proper curative treatments. Numerous studies illustrated the importance of N6-methyladenosine (m6A) RNA modification to tumorigenesis. The aim of this study was to identify novel prognostic signature by using m6A-related lncRNAs, thus to improve the survival for SKCM patients and guide SKCM therapy. METHODS: We downloaded the Presentational Matrix data from The Cancer Genome Atlas (TCGA) and analyzed all the expressed lncRNAs among 468 SKCM samples. Pearson correlation analysis was performed to assess the correlations between lncRNAs and 29 m6A-related genes. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analysis were performed to construct m6A-related lncRNAs prognostic signature (m6A-LPS). The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) survival analysis, univariate COX or multivariate COX analyses. After calculating risk scores, patients were divided into low- and high-risk subgroups by the median value of risk scores. RESULTS: A total of 2973 lncRNAs were found expressed among SKCM tissues. Prognostic analysis showed that 98 lncRNAs had a significant effect on the survival of SKCM patients. The m6A-LPS was validated using K-M and ROC analysis and the predictive accuracy of the risk score was also high according to the AUC of the ROC curve in training and testing sets. A nomogram based on tumor stage, gender and risk score that had a strong ability to forecast the 1-, 2-, 3-, 5-year OS of SKCM patients confirmed by calibrations. Enrichment analysis indicated that malignancy-associated biological processes and pathways were more common in the high-risk subgroup. CONCLUSION: Collectively, m6A-related lncRNAs exert as potential biomarkers for prognostic stratification of SKCM patients and may assist clinicians achieving individualized treatment for SKCM.

Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis.

OBJECTIVE: Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis. METHODS: We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs. RESULTS: Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes. CONCLUSION: Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.

Comparison of characteristics between neuropathic pain and non-neuropathic pain in patients with diabetic carpal tunnel syndrome: A cross-sectional study.

Background: The aim of the study was to compare the clinical characteristics of diabetic carpal tunnel syndrome between patients with neuropathic pain (NeuP) and non-NeuP. Methods: We enrolled 276 patients with diabetic carpal tunnel syndrome. Pain symptoms were evaluated using a visual analog scale. Douleur Neuropathique 4, the Neuropathic Pain Symptoms Inventory questionnaire, and the body map were used to assess neuropathic symptoms. Baseline information, clinical manifestations, electrophysiological test results, and psychological status were compared between the neuropathic pain (NeuP) and non-NeuP to identify the risk factor for NeuP occurrence. Results: Results showed that the degree of pain was more severe in NeuP patients than in nociceptive pain patients (p = 0.025). The frequencies of light touch and pinprick were more pronounced in the NeuP group than in the non-NeuP group (light touch: p = 0.001; pinprick: p = 0.004). There were 48 and 27 NeuP patients with extramedian and proximal spread, respectively, whereas in the non-NeuP group, there were 11 and 9 patients, respectively (p = 0.03). Electrophysiological results showed that patients in the NeuP group exhibited greater sensory nerve conduction velocity impairment compared with the non-NeuP group (p = 0.033). Pain Catastrophizing Scale total scores of the NeuP group were significantly higher than those of the non-NeuP group (p = 0.006). Conclusion: Of the 276 diabetic carpal tunnel syndrome patients studied, the majority had NeuP. Furthermore, light touch, electrophysiological test results, and psychological factors were found to be related to NeuP occurrence in patients with diabetic carpal tunnel syndrome.