Shujing Han

MicroRNA-365a-3p promotes tumor growth and metastasis in laryngeal squamous cell carcinoma

MicroRNAs (miRNAs) are increasingly recognized as oncogenes or tumor suppressors in laryngeal squamous cell carcinoma (LSCC). In this study, we analyzed the roles of miR-365a-3p, miR-143-5p, and miR-494-3p in LSCC using Annexin V/propidium iodide double staining and flow cyto-metry, along with a Transwell migration and invasion assay. The results showed that miR-365a-3p inhibitor significantly facilitated cell apoptosis and suppressed cell cycle progression, migration, and invasion in Hep-2 cells. However, miR-143-5p and miR-494-3p had no such influences. We then investigated the role of miR-365a-3p in LSCC in vivo and found that miR-365a-3p inhibitor suppressed LSCC xenograft tumor growth and metastasis in xenograft mouse models. Moreover, miR-365a-3p inhibitor significantly decreased the expression of p-AKT (Ser473), which indicated that miR-365a-3p can mediate PI3K/AKT signaling pathway transduction via p-AKT (Ser473) in LSCC. The data suggest that miR-365a-3p may act as an oncomiR and may promote growth and metastasis in LSCC via the PI3K/AKT signaling pathway, and thus miR‑365a-3p may be a potential therapeutic target for treatment of LSCC.

Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1.

Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and the most frequently diagnosed cancer in the first year of life. Previous genome-wide association studies (GWAS) of Caucasian and African populations have shown that common single nucleotide polymorphisms (SNPs) in several genes are associated with the risk of developing NB, while few studies have been performed on Chinese children. Herein, we examined the association between the genetic polymorphisms in candidate genes and the risk of NB in Chinese children. In total, 127 SNPs in nine target genes, revealed by GWAS studies of other ethnic groups and four related lincRNAs, were genotyped in 549 samples (244 NB patients and 305 healthy controls). After adjustment for gender and age, there were 21 SNPs associated with NB risk at the two-sided P < 0.05 level, 11 of which were located in LMO1. After correction for multiple comparisons, only rs204926 in LMO1 remained significantly different between cases and controls (OR = 0.45, 95% CI: 0.31–0.65, adjusted P = 0.003). In addition, 16 haplotypes in four separate genes were significantly different between case and control groups at an unadjusted P value < 0.05, 11 of which were located in LMO1. A major haplotype, ATC, containing rs204926, rs110420, and rs110419, conferred a significant increase in risk for NB (OR = 1.82, 95% CI: 1.41–2.36, adjusted P < 0.001). The major finding of our study was obtained for risk alleles within the LMO1 gene. Our data suggest that genetic variants in LMO1 are associated with increased NB risk in Chinese children.

Maternal smoking during pregnancy and risk of childhood neuroblastoma: Systematic review and meta-analysis

BACKGROUND Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma. A meta-analysis was performed statistically surmising all available observational studies on this topic in order to evaluate the potential correlation of maternal smoking during pregnancy and risk of childhood neuroblastoma. METHODS Published literature was obtained from PubMed, Embase, ISI Web of Science, and Cochrane library, and all studies were inclusive until July 2014. Data from epidemiological studies were combined using a general variance-based meta-analytic method employing 95% confidence intervals. The outcome of interest was shown as odds ratio (OR) reflecting the risk of neuroblastoma development associated with smoking while pregnant. Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS Seven case-control studies meeting protocol specified inclusion criteria were obtained through a comprehensive literature search. These studies enrolled a total of 1909 patients and 15,683 controls. Analysis for homogeneity demonstrated that the data were heterogeneous (P < 0.05) and could be statistically combined with randomized effect model. Combining all seven reports yielded an OR of 1.28 (1.01-1.62), a statistically significant result suggesting possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma development (P = 0.005). There was no association between the dosage of maternal smoking during pregnancy and risk of neuroblastoma. CONCLUSION The available epidemiological data support a possible association between maternal smoking during pregnancy and pediatric neuroblastoma development.

Deafness gene mutations in newborns in Beijing.

ABSTRACT Objective To determine the incidence of congenital hearing loss (HL) in newborns by the rate of deafness-related genetic mutations. Design Clinical study of consecutive newborns in Beijing using allele-specific polymerase chain reaction-based universal array. Study sample This study tested 37 573 newborns within 3 days after birth, including nine sites in four genes: GJB2 (35 del G, 176 del 16, 235 del C, 299 del AT), SLC26A4 (IVS7-2 A > G, 2168 A > G), MTRNR1 (1555 A > G, 1494 C > T), and GJB3 (538 C > T). The birth condition of infants was also recorded. Results Of 37 573 newborns, 1810 carried pathogenic mutations, or 4.817%. The carrier rates of GJB2 (35 del G, 176 del 16, 235 del C, 299 del AT), GJB3 (538 C > T), SLC26A4 (IVS7-2 A > G, 2168 A > G), and MTRNR1 (1555 A > G, 1494 C > T) mutations were 0.005%, 0.104%, 1.924%, 0.551%, 0.295%, 0.253%, 1.387%, 0.024%, and 0.274%, respectively. Logistic regression analysis indicated no statistically significant relationship between mutations and infant sex, premature delivery, twin status, or birth weight. Conclusions The 235delC GJB2 mutation was the most frequent deafness-related mutation in the Chinese population. Genetic screening for the deafness gene will help detect more cases of newborn congenital HL than current screening practices.

Investigation of IGF2, IGFBP2 and p63 proteins in rhabdomyosarcoma tumors.

Many efforts have been made to address involvement of the insulin-like growth-factor (IGF) pathway in rhabdomyosarcoma (RMS) pathogenesis, but the actual role of IGF in RMS is still controversial. OBJECTIVE To investigate the implications of IGF2, IGFBP2 and p63 in RMS, and further explored their potential interaction. DESIGN A total of 114 specimens of RMS along with clinic-pathologic characteristics were collected from the year of 2003 to 2013. Protein abundance was detected by immunohistochemical staining, potential relationships between protein levels and clinic-pathological parameters were applied using correlation analysis. RESULTS The results showed positive correlation between IGFBP2 and p63 (r=0.271, p=0.003), suggesting that the interaction of IGFBP2 and p63 might account for the pathogenesis of RMS. In the subtype analysis, positive correlation was still found in embryonal rhabdomyosarcoma (ERMS, r=0.214, p=0.034) and alveolar rhabdomyosarcoma (ARMS, r=0.498, p=0.048). By focusing on the interaction of IGF pathway and p63, our results reveal additional signs to elucidate difference of pathogenesis and severity between ERMS and ARMS. CONCLUSIONS The present study provides novel evidence to elucidate RMS pathogenesis and may be beneficial to clinical diagnosis and therapy for RMS.

Erratum to “The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among Childhood Tuberculosis for Prevalence Surveys in Northern China”

[This corrects the article DOI: 10.1155/2017/5857369.].

Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct

Objectives To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. Methods Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. Results The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. Conclusion In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.

RRS1 gene expression involved in the progression of papillary thyroid carcinoma

BackgroundPapillary thyroid carcinoma (PTC) is one of the most frequent malignancies of the endocrine system, whose mechanisms of pathogenesis, progression and prognosis are still far from being clearly elucidated. Despite an increasing body of evidences highlights ribosome biogenesis regulator homolog (RRS1) as a ribosome biogenesis protein in yeast and plants, little is known about human RRS1 function.MethodsProliferation, cell cycle and apoptosis of PTC cells were assessed following the knockdown of RRS1 expression though MTT, colony formation assay, and flow cytometry. Then, transcriptome profiling was conducted to explore pathway changes after RRS1 silencing in PTC cells. Receiver operating characteristic curve and Youden’s index were performed in twenty-four thyroid carcinoma samples to assess their potential clinical diagnostic value.ResultsFirstly, we found that silencing RRS1 significantly reduced cell proliferation, inhibited cell cycle, and promoted apoptosis in PTC cell line. The result also showed that knock-down of RRS1 could up-regulate genes involving apoptosis and metabolism, while, down-regulate genes relative to cell proliferation and blood vessel development. Notably, the present study confirmed the diagnostic value of RRS1 for thyroid carcinoma in both children and adults.ConclusionsIn conclusion, these data afford a comprehensive view of a novel function of human RRS1 by promoting cell proliferation and could be a potential indicator for papillary thyroid carcinoma.

MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma

BackgroundNeuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood.MethodsQuantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7.ResultsHere we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3′-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB.ConclusionsThese results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.