Glioma, the most common type of primary central nervous system cancers, was progressive with poor survival. MicroRNA, as a novel biomarker, was suspected to be novel biomarkers for glioma diagnosis and prognosis. The study aimed at investigating the diagnostic and predictive value of miR-221/222 family for glioma. In the first phase, we compared plasma miR-221/222 family levels between 50 glioma patients and 51 healthy controls by real-time qRT-PCR amplification. Meanwhile, a meta-analysis based on published studies and presents study was performed to explore the diagnostic performance of miR-221/222 family in human cancers. In the second phase, we correlated the miR-221/222 family expression level with prognosis of glioma using Kaplan-Meier survival curves. The plasma miR-221/222 family levels were found to be significantly upregulated in glioma patients (P = 0.001). The ROC curve analysis yielded an AUC values of 0.84 (95% confidence interval (CI): 0.74-0.93) for miR-221 and 0.92 (95% CI 0.87-0.94) for miR-222. In the meta-analysis, the summary receiver operating characteristic (sROC) was plotted with an AUC of 0.82 (95% CI 0.78-0.85) for miR-221/222 family. It was also demonstrated that high positive plasma miR-221 and miR-222 were both correlated with poor survival rate (miR-221: HR = 2.13; 95% CI, 1.05-4.31; miR-222: HR = 2.09; 95% CI, 1.00-4.37). This study demonstrated that the detection of the miRNA-221/222 family should be considered as a new additional tool to better characterize glioma.

Wnt signaling plays critical roles in dorsoventral fate specification and anteroposterior patterning, as well as in morphogenetic cell movements. Dishevelled proteins, or Dvls, mediate the activation of Wnt/ß-catenin and Wnt/planar cell polarity pathways. There are at least three highly conserved Dvl proteins in vertebrates, but the implication of each Dvl in key early developmental processes remains poorly understood. In this study, we use genome-editing approach to generate different combinations of maternal and zygotic dvl mutants in zebrafish, and examine their functions during early development. Maternal transcripts for dvl2 and dvl3a are most abundantly expressed, whereas the transcript levels of other dvl genes are negligible. Phenotypic and molecular analyses show that early dorsal fate specification is not affected in maternal and zygotic dvl2 and dvl3a double mutants, suggesting that the two proteins may be dispensable for the activation of maternal Wnt/ß-catenin signaling. Interestingly, convergence and extension movements and anteroposterior patterning require both maternal and the zygotic functions of Dvl2 and Dvl3a, but these processes are more sensitive to Dvl2 dosage. Zygotic dvl2 and dvl3a double mutants display mild axis extension defect with correct anteroposterior patterning. However, maternal and zygotic double mutants exhibit most strongly impaired convergence and extension movements, severe trunk and posterior deficiencies, and frequent occurrence of cyclopia and craniofacial defects. Our results suggest that Dvl2 and Dvl3a products are required for the activation of zygotic Wnt/ß-catenin signaling and Wnt/planar cell polarity pathway, and regulate zygotic developmental processes in a dosage-dependent manner. This work provides insight into the mechanisms of Dvl-mediated Wnt signaling pathways during early vertebrate development.

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