Background: Osteoarthritis (OA) is the predominant threaten to the health of the elderly, and it is crucial to understand the molecular pathegenetic mechanisms involved in it. This study aims to investigate the role of a well-studied cancer-related long noncoding RNA (lncRNA)-POU3F3 in OA and its implicated molecular mechanisms. Method: The expression of POU3F3 and miR-29a-3p was examined in osteoarthritis patients, destabilization of the medial meniscus (DMM) mouse OA model, and IL- 1β induced chondrocytes cell OA model by quantitative real-time PCR. The interaction between POU3F3, miR-29a-3p and transcription factor forkhead box O3 (FOXO3) was verified by via dual-luciferase reporter analysis and RNA immunoprecipitation analyses. Cell proliferation and apoptosis were evaluated by cell viability assay and flow cytometry, respectively. Cartilage extracellular matrix (ECM) degradation were investigated with ELISA and western blotting. In addition, the in vivo regulation of POU3F3 in OA was verified by intra-articular injection of lentivirus overexpression POU3F31 in mice models. Results: The expression level of POU3F3 was decreased in OA patients/animal cartilage tissues and IL-1β-stimulated in vitro chondrocyte model. POU3F3 overexpression inhibited IL-1β-induced injury of chondrocytes, enhancing cell viability, suppressing apoptosis and inflammatory cytokine secretion, rescuing metabolic dysfunction, and restrained autophagy in vitro. Mechanistically, Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that miR-29a-3p could directly bind to POU3F3 and FOXO3 was a target gene of miR-29a-3p. Functional rescue assays confirmed this POU3F3/miR-29a-3p/FOXO3 axis in chondrocytes during OA occurrence. Furthermore, intra-articularly delivery of lentivirus containing POU3F3 alleviates the damage in mouse OA model in vivo. Conclusion: this work highlights the function of POU3F3/miR-29a-3p/FOXO3 axis in OA pathogenesis, suggesting this axis as a potential progression of OA [12-15]. These studies indicate the potential contribution of lncRNAs in the development of OA and a promising target for disease diagnosis and treatment.

Background Spindle cell sarcoma is a relatively rare type of sarcoma that mostly originates in soft tissues, but it tends to grow rapidly, and its clinical treatment is a major challenge. From previous reports in the literature, this type of sarcoma has a high proportion of cases affecting the limbs, and research on this topic has potential clinical value. The present study developed a nomogram to effectively predict the survival of patients and analyse the independent prognostic factors of primary limb spindle cell sarcoma.Methods The clinical information of 748 primary limb spindle cell sarcoma patients was obtained from the SEER database. After applying the inclusion/exclusion criteria, 542 patients were included in our study, and they were divided into a training group and a validation group at a ratio of 2:1. The X-tile program was used to determine the best cut-off point for age and tumour size. Univariate and multivariate analyses were used to determine independent prognostic factors, and the training group data were used to construct a nomogram to predict patients’ overall survival and cancer-specific survival. The training cohort data were used for internal verification of the nomogram, and the validation cohort data were used for external verification of the nomogram. The C index was used to calculate the predictive performance of the nomogram. Additionally, we built an online forecasting website.Results The primary limb spindle cell sarcoma has high proportion of all spindle cell sarcoma, and it may have potential associations with pathologic fractures, then marital status, age, historic stage, tumour size and surgical type were identified as five independent prognostic factors, and combined with these factors, a nomogram was constructed for predicting 5-year and 10-year overall survival rates and cancer-specific survival rates. The overall survival rate and tumour-specific survival rate prediction internal validation consistency index (C index) was 0.824 (95% CI 0.794-0.854) and 0.854 (95% CI 0.825-0.883), while the externally validated C index was 0.765 (95% CI 0.706-0.824) and 0.766 (95% CI 0.700-0.832), respectively. Additionally, in order to make the nomogram more convenient and accurate, an online website was created where after entering basic clinical information. The website can help clinicians provide guidance to patients who have these rare sarcomas.Conclusions The nomogram constructed for primary limb spindle cell sarcoma can predict the survival of these patients.