Recently, a cohort of miRNAs, including miR-31, was reported to be downregulated during osteogenic induction by miR microarray analysis. It remains unclear how changes in miR-31 expression collaborate with bone transcription factors to activate the biological pathways that regulate the differentiation of bone mesenchymal stem cells (BMSCs). Here the effects of miR-31, Runx2, and Satb2 on the osteogenic differentiation of BMSCs were investigated using mimics and inhibitors of miR-31, small interfering RNA for knockdown of Runx2 and plasmids for overexpression of Runx2. Our results showed that miR-31 expression decreased progressively in BMSC cultures during differentiation. Inhibition of miR-31 dramatically increased the alkaline phosphatase activity and mineralization in BMSC cultures. Additionally, miR-31 diminished the levels of the Satb2 protein without significantly affecting Satb2 mRNA levels, and Runx2 directly repressed miR-31 expression. Overexpression of miR-31 significantly reduced expression of the osteogenic transcription factors OPN, BSP, OSX, and OCN, but not Runx2. Furthermore, the high expression of miR-31 in BMSCs cultured in the proliferation medium repressed Satb2 protein levels, which may contribute to the maintenance of BMSCs in an undifferentiated state. In conclusion, our results suggest that a Runx2, Satb2, and miR-31 regulatory mechanism may play an important role in inducing BMSC osteogenic differentiation. The results of this study provide us with a better understanding of the molecular mechanisms that govern the BMSC fate.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

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Astrocyte elevated gene-1 (AEG-1) plays an important role in tumor progression including transformation, evasion of apoptosis, invasion, metastasis, and chemoresistance. However, the expression of AEG-1 in ovarian carcinoma and its significance are still unclear. The aim of this study was to examine the expression of AEG-1 in ovarian carcinoma. Immunohistochemistry was performed to determine the expression of AEG-1 in 81 ovarian carcinoma specimens. The correlation of AEG-1 expression with clinicopathological parameters was assessed using χ2 analysis. Patient survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. High expression of AEG-1 was detected in 66.67% of the ovarian carcinomas and was significantly associated with the International Federation of Gynecology and Obstetrics stage, histological grade, presence of residual tumor after primary surgery, and tumor recurrence. Patients with high AEG-1 expression had significantly poorer overall survival and disease-free survival (both P<0.001) when compared with patients with low expression of AEG-1. The multivariate Cox analysis showed that AEG-1 was an independent factor for both overall survival and disease-free survival (both P<0.001). These results showed that high AEG-1 expression was associated with progression and prognosis of ovarian carcinoma.

Recent research has demonstrated critical roles of a number of microRNAs (miRNAs) in stem cell proliferation and differentiation. miRNA-9 (miR-9) is a brain-enriched miRNA. Whether miR-9 has a role in retinal progenitor cell (RPC) proliferation and differentiation remains unknown. In this study, we show that miR-9 plays an important role in RPC fate determination. The expression of miR-9 was inversely correlated with that of the nuclear receptor TLX, which is an essential regulator of neural stem cell self-renewal. Overexpression of miR-9 downregulated the TLX levels in RPCs, leading to reduced RPC proliferation and increased neuronal and glial differentiation, and the effect of miR-9 overexpression on RPC proliferation and differentiation was inhibited by the TLX overexpression; knockdown of miR-9 resulted in increased TLX expression as well as enhanced proliferation of RPCs. Furthermore, inhibition of endogenous TLX by small interfering RNA suppressed RPC proliferation and promoted RPCs to differentiate into retinal neuronal and glial cells. These results suggest that miR-9 and TLX form a feedback regulatory loop to coordinate the proliferation and differentiation of retinal progenitors.

Lysosome-associated protein transmembrane 4β-35 (LAPTM4B-35) is a member of the mammalian 4-tetratransmembrane spanning protein superfamily, which is overexpressed in several solid malignancies. However, the expression of LAPTM4B-35 and its role in the progression of cervical carcinoma is unknown. The aim of this study was to determine the level of expression of LAPTM4B-35 in cervical carcinoma. Immunohistochemistry was used to determine the expression of LAPTM4B-35 protein in 53 cervical intraepithelial neoplasias (CINs) and 113 cervical carcinomas in comparison with 20 normal cervical specimens. The correlation between the expression of the LAPTM4B-35 protein and the clinicopathologic characteristics of patients with cervical carcinoma was analyzed. Statistical analysis showed that LAPTM4B-35 expression was significantly elevated in CINII/III and cervical carcinoma but not in CINI compared with the normal controls (P=0.002, P<0.001 and P=0.289, respectively). In addition, the LAPTM4B-35 expression was significantly higher in both the CINII/III and cervical carcinoma cases than in the CINI cases (P=0.021 and P=0.002, respectively). High LAPTM4B-35 staining was present in 72.57% (82 of 113) of all the cases with cervical carcinoma. The overexpression of LAPTM4B-35 was significantly associated with the International Federation of Gynecology and Obstetrics stage (P=0.014), tumor histologic grade (P=0.033), lymph node metastasis (P=0.045), and recurrence (P=0.010). The Kaplan-Meier survival analysis showed that the high expression of LAPTM4B-35 was related to the poor overall survival and disease-free survival of patients with cervical carcinoma (P=0.004 and P=0.005, respectively). Multivariate Cox analysis showed that LAPTM4B-35 was an independent factor for both overall survival and disease-free survival (P=0.015 and P=0.016, respectively). Overexpression of LAPTM4B-35 may be associated with tumor progression in cervical carcinoma and thus may serve as a new molecular marker to predict the prognosis of cervical carcinoma patients.

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4 beta) plays several crucial roles in carcinogenesis. In this case-control study, we investigated the relationship between LAPTM4B gene polymorphism and susceptibility to endometrial carcinoma (EC). In an adjusted multivariate logistic regression analyses, subjects with the LAPTM4B*1/2 and *2/2 genotypes respectively exhibited 1.572-fold (95% confidence interval (CI) = 1.041-2.375) and 2.335-fold (95% CI = 1.365-3.995) increases in the risk of developing EC relative to those carrying LAPTM4B*1/1. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both p < 0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both p < 0.001). These results suggest that LAPTM4B polymorphisms might play an important role in the aetiology of EC.