MiR-29b-3p cooperates with miR-29c-3p to affect the malignant biological behaviors in T-cell acute lymphoblastic leukemia via TFAP2C/GPX1 axis.

Mounting evidence has illustrated the tumor regulatory roles of microRNAs (miRNAs) in T-cell acute lymphoblastic leukemia (T-ALL), a malignant carcinoma originated from T-cell precursors. However, the possible regulation mechanisms underlying miR-29b/29c-3p in T-ALL have not been interrogated yet. The aim of our study was to probe the association and possible molecular mechanism of miR-29b/29c-3p and Glutathione Peroxidase 1 (GPX1), a predicted highly expressed gene in acute myeloid leukemia (LAML) tissues on the cancer genome atlas (TCGA) website. In our paper, it was observed that GPX1 was relatively overexpressed in T-ALL cells, compared with normal T cells. Loss-of-function assays demonstrated that GPX1 knockdown inhibited the proliferation and activated the apoptosis in T-ALL cells. Then miR-29b/29c-3p was confirmed to regulate GPX1 mRNA and protein expression via decreasing Transcription Factor AP-2 Gamma (TFAP2C) expression. In summary, miR-29b-3p and miR-29c-3p targeted TFAP2C so as to repress GPX1 transcription, thereafter inhibiting GPXA expression. In the end, rescue experiments proved the whole regulation mechanism of miR-29b/29c-3p in T-ALL. Overall, the miR-29b/29c-3p -TFAP2C-GPX1 axis helped us to have a better understanding of T-ALL pathogenesis.

A novel mutation of SGSH and clinical features analysis of mucopolysaccharidosis type IIIA.

RATIONALE: The aim of this study was to analyze the clinical and imaging features of a pediatric patient with mucopolysaccharidosis type IIIA (MPS IIIA) and a novel mutation of the N-sulfoglucosamine sulfohydrolase (SGSH) in 1 pedigree. PATIENT CONCERNS: An 8-year-old female patient presented with developmental regression, seizures, cerebral atrophy, thickened calvarial diploe, apathy, esotropia, slender build, thick hair, prominent eyebrows, hepatomegaly, ankle clonus, muscle and joint contractures, and funnel chest. DIAGNOSES: The patient was diagnosed as autosomal recessive (AR) MPS IIIA with a novel mutation in the SGSH gene. INTERVENTIONS: Genomic DNA was extracted from the peripheral blood and next-generation sequencing (NGS) technology was used to detect pathogenic genes, and the Sanger method was applied to perform pedigree verification for the detected suspicious pathogenic mutations. OUTCOMES: The NGS done for the girl and her family showed 2 variations that were both missense mutations in SGSH. The c.1298G > A (p.Arg433Gln) was a known mutation, and the c.630 G > T (p.Trp210Cys) was a novel variation. LESSONS: The common clinical manifestations of MPS IIIA were rapid developmental regression, seizures, cerebral atrophy, and thickened calvarial diploe. The results showed that the c.630 G > T was likely pathogenic according to bioinformatics analysis, which probably was a novel mutation. This study reports 1 case of MPS IIIA with some clinical features as determined via clinical and genetic analysis, and found a new mutation in the SGSH gene.