Previous study revealed that microRNA (miR)-150 might function as a tumor suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in 20 osteosarcoma and matched adjacent noncancerous tissues were respectively detected by quantitative real-time PCR and western blot analyses. Then, subcellular localization and expression pattern of IGF2BP1 protein in 100 osteosarcoma tissues were examined by immunohistochemistry. Associations of miR-150/IGF2BP1 expression with various clinicopathological features and patients' prognosis were also statistically evaluated. As a result, miR-150 expression was significantly decreased, while IGF2BP1 mRNA and protein expression were dramatically increased in osteosarcoma tissues compared to matched adjacent noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all significantly associated with high tumor grade, presence of metastasis and recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover, miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as independent prognostic factors for overall and disease-free survivals of osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR-150 and its downstream target IGF2BP1 may be a crucial axis for the development, progression and patients' prognosis of ostesarcoma. The newly identified miR-150/IGF2BP1 axis might be a novel potential therapeutic target for osteosarcoma treatment.
Background Tendon-ligament injuries (TLIs), including Achilles tendinopathy, cruciate ligament injury, tennis elbow, rotator cuff injury, patellar tendinopathy, and tibial tendinopathy, are common musculoskeletal soft injuries during physical activity. Matrix metalloproteinase-3 (MMP-3) gene polymorphisms have been implicated in the etiology of TLIs in several genetic association studies with inconsistent results. The purpose of this study was to collect and synthesize the current evidences on the association of MMP-3 polymorphisms and TLIs. Methods The search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang databases, prior to July, 2021. Newcastle Ottawa Scale was used to appraise the study quality. Strengths of association were represented by odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Thirteen studies with 2871 cases and 4497 controls met the eligibility criteria, and each study was in high quality. The overall analyzes suggested rs3025058 was associated with an increased TLIs risk (5A vs. 6A, OR = 1.20, 95% CI 1.03–1.40, P = 0.020). However, the association was not found for rs679620, rs591058, and rs650108 polymorphisms. Subgroup analysis by injury type suggested that rs679620 polymorphism was associated with a reduced risk to Achilles tendon rupture (AA + AG vs. GG, OR = 0.46, 95% CI 0.25–0.87, P = 0.020), and rs3025058 was associated with an elevated risk to anterior cruciate ligament injury (5A5A + 5A6A vs. 6A6A, OR = 1.46, 95% CI 1.03–2.06, P = 0.030). When stratified by ethnicity, the findings indicated that rs3025058 polymorphism was associated with an increased TLIs risk among Caucasians (5A6A vs. 6A6A, OR = 1.55, 95% CI 1.09–2.42, P = 0.020) and Brazilians (5A5A vs. 5A6A + 6A6A, OR = 2.80, 95% CI 1.44–5.45, P = 0.002). Conclusion Findings of this study suggest that rs679620 polymorphism is associated with a reduced Achilles tendon rupture risk, and rs3025058 polymorphism contributes to an increased TLIs risk in Caucasians and Brazilians. However, rs591058 and rs650108 polymorphisms do not show any association with TLIs.
Objective Inconsistent findings existed on the correlation of collagen type V α1 (COL5A1) gene polymorphisms and musculoskeletal soft tissue injuries (MSTIs). The purpose of this study was to collect and combine the current evidences by a meta-analysis approach. Methods Six online databases were searched up to August, 2021. The methodological quality of each individual study was evaluated based upon Newcastle–Ottawa Scale (NOS). The strength of the effect size was presented by odds ratio (OR) with 95% confidence interval (95%CI) in five genetic models. The data were analyzed using Review Manager 5.3. Results Twenty-one studies were eligible to this meta-analysis. The study quality was deemed fair to excellent according to NOS. In the overall analyses, the merged data suggested that rs12722, rs71746744, and rs3196378 polymorphisms were correlated to an increased susceptibility to MSTIs. But the association was not established in rs13946 or rs11103544 polymorphism. For rs12722 polymorphism, stratified analyses by injury type and ethnicity identified the association mainly existed in ligament injury and among Caucasian population. For rs13946 polymorphism, subgroup analysis suggested the association existed in tendon and ligament injuries. Conclusion This study supports that rs12722 is associated with an elevated susceptibility to ligament injury, especially in the Caucasian population. Rs13946 polymorphism appears to increase the risk to tendon and ligament injuries. Rs71746744 and rs3196378 polymorphisms have a tendency to confer an elevated risk to MSTIs. However, no relevance is found between rs11103544 polymorphism and MSTIs.
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