We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR‐8075, which targeted TPX2 in cervical cancer cells. We showed that miR‐8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996‐mediated inhibition of miR‐8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996‐miR‐8075‐TPX2 network promoted cervical cancer progression.

BackgroundGastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC.MethodsAQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines.ResultsAQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC.ConclusionsAQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment.

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This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103 AMI patients, 149 non-AMI subjects, and 95 healthy volunteers. We found that only two of them, Zinc finger antisense 1 (ZFAS1) and Cdr1 antisense (CDR1AS), showed significant differential expression between AMI patients and control subjects. Circulating level of ZFAS1 was significantly lower in AMI (0.74 ± 0.07) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001), whereas CDR1AS showed the opposite changes with its blood level markedly higher in AMI (2.18 ± 0.24) than in non-AMI subjects (1.0 ± 0.05, P < 0.0001). When comparison was made between AMI and non-AMI, the area under ROC curve was 0.664 for ZFAS1 alone or 0.671 for CDR1AS alone, and 0.691 for ZFAS1 and CDR1AS combination. Univariate and multivariate analyses identified these two lncRNAs as independent predictors for AMI. Similar changes of circulating ZFAS1 and CDR1AS were consistently observed in an AMI mouse model. Reciprocal changes of circulating ZFAS1 and CDR1AS independently predict AMI and may be considered novel biomarkers of AMI.Acute myocardial infarction (AMI) is the worst threat to human lives and the quality of human life. Early detection of AMI with noninvasive and reliable biomarkers is the foremost step for minimizing ischemic damage to the myocardium. Clinically validated biomarkers like creatine kinase MB (CKMB) and cardiac troponin I (cTnI), currently considered as "gold standard" for AMI diagnosis [1][2][3][4] , have a number of pitfalls. Search for new biomarkers of AMI, particularly those for early diagnosis, is therefore a top-urgent mission and has actually been an endless effort from fundamental and clinical researchers worldwide.In addition to protein biomarkers, recent studies have suggested the potential value of RNA biomarkers for AMI, e.g., microRNAs (miRNAs) [5][6][7] . More recently, long non-coding RNAs (lncRNAs), a new class of functional

Genome-editing involves the insertion, deletion, or replacement of DNA in the genome of a living organism using “molecular scissors.” Traditional genome editing with engineered nucleases for human stem cells is limited by its low efficiency, high cost, and poor specificity. The CRISPR system has recently emerged as a powerful gene manipulation technique with advantages of high editing efficiency and low cost. Although this technique offers huge potential for gene manipulation in various organisms ranging from prokaryotes to higher mammals, there remain many challenges in human stem cell research. In this review, we highlight the basic biology and application of the CRISPR/Cas9 system in current human stem cell research, discuss its advantages and challenges, and debate the future prospects for human stem cells in regenerative medicine.

Patients diagnosed with metastatic breast cancer have a dismal 5-year survival rate of only 24%. The RNA-binding protein Hu antigen R (HuR) is upregulated in breast cancer, and elevated cytoplasmic HuR correlates with high-grade tumors and poor clinical outcome of breast cancer. HuR promotes tumorigenesis by regulating numerous proto-oncogenes, growth factors, and cytokines that support major tumor hallmarks including invasion and metastasis. Here, we report a HuR inhibitor KH-3, which potently suppresses breast cancer cell growth and invasion. Furthermore, KH-3 inhibits breast cancer experimental lung metastasis, improves mouse survival, and reduces orthotopic tumor growth. Mechanistically, we identify FOXQ1 as a direct target of HuR. KH-3 disrupts HuR-FOXQ1 mRNA interaction, leading to inhibition of breast cancer invasion. Our study suggests that inhibiting HuR is a promising therapeutic strategy for lethal metastatic breast cancer.