MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1

Background MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated. Methods MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay. Results Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 30-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples. Conclusion This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM

Identifying the Lowest Effective Initial Dose of Prednisolone for the Treatment of Subacute Granulomatous Thyroiditis: A Systematic Review and Meta-Analysis

BACKGROUND: Subacute granulomatous thyroiditis (SAGT) is an inflammatory disease due to viral infections. Glucocorticoids, especially prednisolone (PSL), are one of the first approaches in the treatment of patients with SAGT. To date, no study has determined the lowest effective dose of prednisolone with the lowest recurrence rate in the treatment of SAGT. This study aimed to use meta-analysis methods to identify the appropriate dosage of prednisolone with the lowest recurrence rate in the treatment of patients with SAGT. METHODS: This study was conducted according to the PRISMA checklist in February 2021. Two independent researchers performed a search for relevant literature published before March 2021 in English databases including Scopus, MEDLINE (via PubMed), Web of Science, Cochrane Library, Google Scholar, EMBASE, and also Persian electronic databases including SID, Iran medex, Magiran, and Irandoc. The search algorithm was initially developed by using a combination of MeSH terms, keywords, and also Boolean operators ("AND"; "OR"; "NOT"): Subacute thyroiditis, De Quervain Thyroiditis, Glucocorticoids, Prednisolone, Recurrence, and Meta-Analysis. All statistical analyses were performed using STATA 15.0 (StataCorp LLC, College Station, TX, USA) and SPSS 17.0. A random-effects model based on Metaprop were applied for the Meta-analysis. To assess heterogeneity between studies, the chi-squared test and I2 index were used, and for evaluating publication bias, funnel plots and Egger tests were performed. RESULTS: The overall recurrence rate was 14.72 95% CI: 9.63- 20.58 and there was a significant heterogeneity among the studies I2 = 69.56%; P=0.000. To evaluate the lowest effective dose of prednisolone, we divided the studies into two groups based on the mean initial dose of prednisolone: less than or equal to 20 mg/day (group one) and greater than 20 mg/day (group two). The recurrence rate in group 1 was 11% 95% CI: 5.7- 16.2 and in group 2 was 23.6% 95% CI: 11.5- 35.6. Significant correlations were observed between the initial mean dose of PSL and recurrence rate (r= 0.71; P= 0.013). Begg's funnel plot there was no evidence of publication bias in these studies (p=0.160). CONCLUSION: According to the results of this meta-analysis, 15 to 20 mg/day of prednisolone is the most effective dosage with the lowest recurrence rate in the treatment of subacute Granulomatous thyroiditis