Aggressive Medulloblastoma-Derived Exosomal miRNAs Promote In Vitro Invasion and Migration of Tumor Cells Via Ras/MAPK Pathway.

Medulloblastomas (MBs) are currently divided into 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Among them, Group 3 MB has the worst prognosis, and 40%-50% of Group 3 cases are already metastatic at the time of diagnosis. Emerging evidence indicates that exosomes drive tumor invasion, but very little is known about exosomes in MBs. In this study, we initially discovered that exosomes isolated from Group 3 MB cell lines altered in vitro behaviors of a less invasive SHH MB cell line and yielded a much more aggressive phenotype. RNA-sequencing analysis revealed 7 exosomal miRNAs with markedly different expression levels between the SHH and Group 3 MB cell lines. They were all predicted to be related to the Ras/MAPK pathway according to the Kyoto Encyclopedia of Genes and Genomes data analysis. Increased expression of miR-181a-5p, miR-125b-5p, and let-7b-5p was further confirmed in Group 3 MB cells with real-time PCR and was shown to increase in vitro invasion and migratory abilities of tumor cells through the activation of ERK in Ras/MAPK pathway. Collectively, our findings suggest that exosomal miRNAs have a critical role in MB progression in vitro and might serve as diagnostic biomarkers and therapeutic targets.

[Meta analysis and analytic hierarchy process-based intervention strategy research of acupuncture for primary depressive disorder].

OBJECTIVE: To acquire the optimal intervention methods of acupuncture on primary depressive disorder (PDD) through high quality clinical evidences of acupuncture for PDD and analytic hierarchy process. METHODS: Databases of domestic and international medical literatures were retrieved with computer. And high-quality clinical evidences on treatment of PDD with acupuncture were collected. Jadad scale evaluation was adopted to estimate the quality of evidences. RevMan 5.1 software was applied for Meta analysis and statistical appraisal on effect size. Analytic hierarchy process was utilized on acquired clinical evidences to construct the model and matrix to screen the optimal interevention method. RESULTS: Fourteen researches were included. And the result of Meta analysis showed that no statistical differences could be found on clinical control rate, marked effectiveness rate, effective rate and the overall clinical effective rate between acupuncture and selective serotonin reuptake inhibitor (SSRIs). The combination of acupuncture and SSRIs could improve the clinical control rate and the overall clinical effective rate. And a 6-week intervention of electro-acupuncture combined with SSRIs was considered as the best intervention for the best overall effect. CONCLUSION: Based on the present clinical evidences, a 6-week intervention of acupuncture combined with SSRIs is the best intervention on mild or moderate PDD, which can obviously enhance the clinical control rate and the overall clinical effective rate.