Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3'UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.

OBJECTIVE To investigate the effects of miR-671-3p on the proliferation and invasion of breast cancer cells and explore the possible mechanism. METHODS We examined the expressions of miR-671-3p in human normal epithelial cells (MCF-10A) and breast cancer cell lines (MCF-7, MDA-MB-231, and SK-BR3) using RT-PCR. The effects of transfection with a miR-671-3p mimic or inhibitor on the proliferation, migration and invasion of MCF-7 cells were evaluated using CCK-8 assay and Transwell chamber assay. The target gene of miR-671-3p was predicated with Targetscan and validated by a dual luciferase reporter system and Western blotting. RESULTS The expression of miR-671-3p was significantly lower in breast cancer cells than in normal breast epithelial cells. Compared with negative control group, MCF-7 cells with miR-671-3p overexpression exhibited significantly reduced proliferation and invasion, whereas inhibition of miR-671-3p obviously promoted the cell proliferation and invasion. Luciferase reporter assay demonstrated that DEPTOR was the target gene of miR-671-3p, and miR-671-3p overexpression caused significant down-regulation of the protein expression of DEPTOR. CONCLUSIONS MiR-671-3p suppresses the proliferation and invasion of breast cancer cell line MCF-7 by directly targeting DEPTOR protein.

BACKGROUND:MicroRNAs are a class of small non-coding RNAs that are involved in many important physiological and pathological processes by regulating gene expression negatively. The purpose of this study was to investigate the effect of miR-32 on cell proliferation, migration and apoptosis and to determine the functional connection between miR-32 and FBXW7 in breast cancer.METHODS:In this study, quantitative RT-PCR was used to evaluate the expression levels of miR-32 in 27 breast cancer tissues, adjacent normal breast tissues and human breast cancer cell lines. The biological functions of miR-32 in MCF-7 breast cancer cells were determined by cell proliferation, apoptosis assays and wound-healing assays. In addition, the regulation of FBXW7 by miR-32 was assessed by qRT-PCR, Western blot and luciferase reporter assays.RESULTS:MiR-32 was frequently overexpressed in breast cancer tissue samples and cell lines as was demonstrated by qRT-PCR. Moreover, the up-regulation of miR-32 suppressed apoptosis and promoted proliferation and migration, whereas down-regulation of miR-32 showed an opposite effect. Dual-luciferase reporter assays showed that miR-32 binds to the 3'-untranslated region of FBXW7, suggesting that FBXW7 is a direct target of miR-32. Western blot analysis showed that over-expression of miR-32 reduced FBXW7 protein level. Furthermore, an inverse correlation was found between the expressions of miR-32 and FBXW7 mRNA levels in breast cancer tissues. Knockdown of FBXW7 promoted proliferation and motility and suppressed apoptosis in MCF-7 cells.CONCLUSIONS:Taken together, the present study suggests that miR-32 promotes proliferation and motility and suppresses apoptosis of breast cancer cells through targeting FBXW7.

Number of studies assessed the association between Cytotoxic T lymphocyte antigen-4 (CTLA-4) -1722T/C polymorphisms and systemic lupus erythematosus (SLE) was increasing. However, these studies have provided conflicting results. In this study, meta-analysis was performed to invest the correlation between CTLA-4 -1722T/C polymorphisms and SLE susceptibility. Eligible case-control studies published up to June 2015 were selected from PubMed, EMBASE, MEDLINE, CNKI and WanFang databases. Meta-analysis was performed using Stata12.0 software to analyze the data according to the inclusion and exclusion criteria. A total of 11 studies comprising 1722 SLE cases and 1829 controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. In addition, Begg's test was used to measure publication bias. The meta-analysis results demonstrated that there was significant association between CTLA-4-1722T/C polymorphisms and SLE susceptibility (TT+TC vs. CC: OR=1.80, 95% CI=1.15-2.80, P<0.05; TT vs. TC+CC: OR=1.39, 95% CI=1.04-1.85, P<0.05; TT vs. CC: OR=2.05, 95% CI=1.24-3.38; TC vs. CC, OR=1.62, 95% CI=1.06-2.49, P<0.05). When stratified by ethnicity, the association still existed for Asian population (T vs. C: OR=1.50, 95% CI=1.15-1.95, P<0.01), but no significant correlation existed for Europeans and Africans groups. In suumary, there is a significant association between CTLA-4-1722T/C gene polymorphisms and SLE susceptibility.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is important for the down regulation of T-cell activation. Number of studies assessed the association between CTLA-4 −318C/T polymorphisms and cancer in different populations. However, the studies have provided conflicting results. We performed a meta-analysis to examine the association between CTLA-4 −318C/T polymorphisms and cancer susceptibility. Eligible studies were identified by searching several databases for relevant reports published up to September 30, 2012. Sixteen eligible studies with a total of 6190 patients and 6560 controls were included to summarize the association between CTLA-4 −318C/T polymorphisms and the risk of cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Overall, no significant associations were found in all genetic models when all studies were pooled into the meta-analysis (for −318C/T polymorphisms as estimated using a fixed effect model: TT vs. (CC 1 CT), OR = 1.02, 95% CI = 0.83–1.24; (TT 1 CT) vs. CC, OR = 1.20, 95% CI = 1.00–1.44; TT vs. CC, OR = 1.09, 95% CI = 0.74–1.59; CT vs. CC, OR = 1.21, 95% CI = 1.00–1.46). In further subgroup analyses for the −318C/T polymorphisms, stratified by design of ethnicity, cancer types, solid tumors to non-solid tumors, epithelial tumors to non-epithelial tumors, no significant associations were found in any subgroup of the population. This meta-analysis strongly suggests that −318C/T polymorphisms in CTLA-4 are not associated with an increased risk of cancer.