von Willebrand factor rescued by miR-24 inhibition facilitates the proliferation and migration of osteosarcoma cells in vitro

Abstract

von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has been unclear yet. The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labeling and quantitative real-time PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS cells were assessed by cell proliferation, colony formation, and migration. The clinical significance of miR-24 in OS patients was analyzed using Kaplan–Meier analyses and Pearson’s Chi-squared test. Here, we reported that the expression of vWF was significantly increased, but miR-24 was significantly decreased in OS tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63 and U2OS cells. However, the migration-inhibiting activity of miR-24 was predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression in human OS tissues was significantly associated with tumor metastasis and predicted a poor survival in OS patients. This work demonstrated that vWF, as a downstream effector of miR-24, played an important role in controlling OS cell progression. Target miR-24 or vWF, therefore, promises to be an effective biological target for OS treatment.

MiR-24-3p and various cancers: From a meta-analysis view

“…The overall sample size is 1518 patients coming from 25 to 247 which from 4 countries. Among these studies, several types of cancer include lung cancer (n = 3) [33][34][35], hepatocellular carcinoma (n = 2) [36,37], colorectal cancer (n = 2) [29,38], nasopharyngeal carcinoma (n = 2) [39,40], osteosarcoma (n = 1) [41], ALL (n = 1) [42], AML (n = 1) [42], advanced gastric cancer (n = 1) [28], esophageal cancer (n = 1) [43], head and neck squamous cell carcinoma (n = 1) [44]. As for OS, RFS and DFS, there were seven studies directly provide HRs and its 95% CI [28,29,[35][36][37][38][39].…”

“…As for OS, RFS and DFS, there were seven studies directly provide HRs and its 95% CI [28,29,[35][36][37][38][39]. In addition, the remaining eight studies only provided Kaplan-Meier curves [28,33,34,[40][41][42][43][44]. All studies measured the miR-24-3p expression level by qRT-PCR (quantitative real-time polymerase chain reaction).…”

“…Second, the sensitivity analysis was used, but no outlier was identi ed to impact on the pooled results signi cantly. Third, two studies were identi ed as outliers by publication bias evaluation (Liu et al [41] and Gao et al [29]). After retrieving the data of outliers, we found that the specimen recruited in them were all from Asian (Chinese), tissue and the sample size less than 100 which all have strong heterogeneity.…”

“…After retrieving the data of outliers, we found that the specimen recruited in them were all from Asian (Chinese), tissue and the sample size less than 100 which all have strong heterogeneity. Besides, Liu et al [41] was the sole study that focused on the Osteosarcoma and Gao et al [29] had an opposite conclusion with Kerimis et al [38] who also investigated the miR-24-3p expression levels to colorectal cancer. After removing those two outliers, greatly declined of the heterogeneity was observed.…”

“…Next, funnel plots, Begg's test and Egger's test were implemented to assess the potential publication bias and two studies as the outliers were identi ed eventually (Figure. 2d) (Liu et al [41] and Gao et al [29] ). After removing them, dramatically decline of the heterogeneity was observed (I 2 = 34.60%, P = 0.141) in the overall analysis, and the signi cance of the prognostic effects of miR-24-3p expression was still obvious (Figure.…”