Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit a higher rate of glucose uptake, which is accompanied with the metabolic switch from oxidative phosphorylation to aerobic glycolysis. The metabolic reprogramming of cancer cell supports excessive cell proliferation, which are frequently mediated by the activation of oncogenes or the perturbations of tumor suppressor genes. Recently, a growing body of evidence has started to reveal that long noncoding RNAs (lncRNAs) are implicated in a wide spectrum of biological processes in glioma, including malignant phenotypes and aerobic glycolysis. However, the mechanisms of diverse lncRNAs in the initiation and progression of gliomas remain to be fully unveiled. In this review, we summarized the diverse roles of lncRNAs in shaping the biological features and aerobic glycolysis of glioma. The thorough understanding of lncRNAs in glioma biology provides opportunities for developing diagnostic biomarkers and novel therapeutic strategies targeting gliomas.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder with a genetic origin. The purpose of the present study was to analyze the mutation spectrum of CH patients in China. A targeted next‑generation sequencing panel covering all exons of 29 CH‑related causative genes was used in 43 Han Chinese patients with CH [11 dysgenesis and 32 glands in situ (GIS)]. The functional impact and pathogenicity of detected variants were analyzed using a comprehensive bioinformatics approach and co‑segregation studies. A total of 47 rare non‑polymorphic variants in 9 target genes associated with thyroid hormone synthesis (DUOX2, DUOXA2, TPO, TG, SLC26A4 and SLC5A5), thyroid stimulating hormone resistance (TSHR) and central hypothyroidism (PROP1 and TRHR) were identified in 31 patients (31/43, 72%). Of these variants, 8 were novel, including 3 in DUOX2, 2 in TPO, 3 in TSHR and 1 in SLC5A5. Variants were mostly affected by DUOX2, TG, TPO and TSHR. Approximately 44% of the patients (19/43) carried DUOX2 variants. The mutation detection rates in patients with GIS were higher compared with patients with dysgenesis [25/32 (78%) vs. 6/11 (54%)]. Oligogenic mutations were detected in 25.6% of the total cases and 35% of the mutated cases. Genetic basis was ascertained in 13 patients, reaching a diagnosis detection rate of 30%. In conclusion, genetic defects in dyshormonogenesis, mainly in DUOX2, were the main genetic cause of CH in the Chinese population. Oligogenicity is highly involved in CH pathogenesis and may thus be an important factor in common phenotypic variability observed in patients with CH.

Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status. IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated. Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However, only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1 displayed higher ZIP11 expression than those without IDH1 mutations. This finding indicated that zinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathways or genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4 and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailed biological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1 mutation in gliomagenesis should be further investigated.

Objective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results. Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions. DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study.