Objective. MicroRNA (miRNA) have received increasing attention as posttranscriptional regulators that fine-tune the homeostasis of the inflammatory response. This study aimed to clarify whether miR-125a, which was identified in a pilot expression profiling step, is involved in the inflammatory chemokine pathway in systemic lupus erythematosus (SLE).Methods. Independent verification of miR-125a expression in amplified samples from SLE patients and normal controls was performed by TaqMan quantitative polymerase chain reaction (PCR) analysis. A combination of 3 bioinformatic prediction techniques and reporter gene assays was used to identify miR-125a targets. In vitro systems of overexpression by transfection and inducible expression by stimulation were performed to investigate the function of miR-125a, which was followed by real-time quantitative PCR and enzymelinked immunosorbent assay.Results. In SLE patients, the expression of miR125a was reduced and the expression of its predicted target gene, KLF13, was increased. Bioinformatics predicted that miR-125a base-paired with sequences in the 3 -untranslated region of KLF13. Overexpression of miR-125a led to a significant reduction in the expression of RANTES and KLF13. MicroRNA-125a inhibited endogenous KLF13 expression in a dose-dependent manner, as determined using gain-and loss-of-function methods. A luciferase reporter system confirmed the miR-125a binding sites. Notably, miR-125a expression was induced in T cells in a dose-and time-dependent manner. Finally, the introduction of miR-125a into T cells from SLE patients alleviated the elevated RANTES expression.Conclusion. MicroRNA-125a negatively regulates RANTES expression by targeting KLF13 in activated T cells. The underexpression of miR-125a contributes to the elevated expression of RANTES in SLE. Our findings extend the role of miRNA in the pathogenesis of lupus and provide potential strategies for therapeutic intervention.

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.

AIM:To investigate the expression of annexin I in pancreatic cancer and its relationship with the clinicopathologic factors, and to evaluate its potential clinical significance.

Although the incidence of colorectal cancer is steadily increasing, screening for colorectal cancer with conventional approaches is not routinely performed in China. Noninvasive screening methods are attractive options to resolve this issue. is frequently methylated in colorectal cancer. However, the value of a stool test of methylated for the detection of colorectal cancer is unknown. Methylation status of was tested in cell lines and 398 colorectal tissue samples and further evaluated with 497 stool samples, including 196 from colorectal cancer patients, 122 from adenoma patients, and 179 from normal individuals, using real-time methylation-specific PCR. The impacts of one quantitative partial stool sampling device and 17 potentially interfering substances on the performance of fecal methylated were also analyzed. expression was also measured. methylation level was higher in 96.8% (120/124) of colorectal cancer tissues compared with paired adjacent normal epithelia. Stool test of methylated detected 81.1% (159/196) of colorectal cancer and 58.2% (71/122) of adenomas at a specificity of 93.3% (167/179). No significant difference was found between partial and whole stool collection on colorectal cancer detection ( > 0.05, = 0.80). Among 17 interfering substances, only berberine at high concentrations inhibited fecal detection of methylated was overexpressed in colorectal cancer tissues compared with normal epithelia. Fecal methylated is a valuable biomarker for the noninvasive detection of colorectal neoplasms. Stool DNA test of methylated would serve as an alternative method for screening colorectal neoplasms..

Over the past several years, long non‐coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11‐AS was much stronger in cisplatin‐resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11‐AS had shorter survival time. Additionally, knockdown of HOXA11‐AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11‐AS/miR‐454‐3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11‐AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11‐AS, miR‐454‐3p and Stat3. In conclusion, lncRNA HOXA11‐AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR‐454‐3p/Stat3 axis.

Quantum dots (QDs) have emerged as a new class of fluorescent label with unique optical properties. 1 Recent advances in watersoluble and bioconjugated QDs have made them very appealing for biosensing and bioimaging. 2-11 Among these, QDs with CdSe core and ZnS shell have been the most used optical material for bioconjugation. However, CdSe/ZnS core-shell QDs are synthesized in organic medium and contain a layer of outside capping ligand of tri-n-octylphosphine oxide (TOPO), 12,13 which makes them insoluble in aqueous solution. Different methods have been developed to make CdSe/ZnS QDs water-soluble so that biomolecules can be either covalently or noncovalently attached to the surface of QDs. 9,10 In the early development of water-soluble QDs, water-soluble CdSe/ZnS QDs were generated by ligand exchange of TOPO with mercaptocarbonic acid, 3,9 which ought to be greatly advantageous due to its simplicity. The carboxylic acid group was further coupled with various biomolecules. However, it was found that the quantum yield (QY) of the QDs after the ligand exchange dropped significantly. 14 Although the mechanism of the PL decrease is still not clear, it has been attributed to ligand exchange between the new ligand and the original capping TOPO molecules, during which surface defects might be generated. 15 Herein we report a new and simple method that allows simultaneous in situ functionalization of CdSe QDs by mercaptocarbonic acid and surface passivation by a thin ZnS shell. This method avoids the second-step ligand exchange after the coreshell formation and yet preserves high QY and stability of the QDs. We demonstrated that such prepared QDs can serve as an excellent nanomaterial for bioconjugation. Different antibodies were conjugated to the mercaptopropyl acid (MPA)-functionalized QDs and resulted in highly stable and highly photoluminescent nanoparticles for cell labeling purposes.Scheme 1 illustrates our new scheme of QD preparation (Scheme 1b) and its comparison to the conventional TOPO-MPA ligand exchange method (Scheme 1a). In this new method, the starting oleylamine-capped CdSe QDs were prepared using our previously reported low-temperature synthesis method; 16 the preparation of the CdSe/ZnS core-shell QDs capped with MPA is achieved in a single step by in situ shell formation and ligand capping. This new strategy allows that ZnS shell formation and MPA functionalization to be executed simultaneously. By doing so, the ligand exchange step (Scheme 1a) can be eliminated. We found that this method preserves the photoluminescence (PL) intensity of the core-shell QDs in contrast to the case of the water-soluble QDs prepared by the conventional method through ligand exchange. Figure 1a compares the QY of the MPA-functionalized CdSe/ ZnS prepared by the two methods along with TOPO-capped core/ shell product. The QY of MPA-capped CdSe/ZnS QDs is comparable with TOPO-capped CdSe/ZnS QDs produced by our new method. In contrast, the QY of MPA-capped CdSe/ZnS QDs produced using the ligand exchange method was lower by...

Increasing evidence suggests that dysregulation of microRNAs is correlated with malignant transformation and tumor development. miR-100, a potential tumor suppressor, is downregulated by many human cancers. However, the expression and functions of miR-100 in hepatocellular carcinoma (HCC) are still unclear. The aim of this study was to detect the expression of miR-100 in HCC tissues and investigate its clinicopathological and prognostic significance. Also, the effects of miR-100 on growth and apoptosis of HCC cells and its potential molecular mechanisms were analyzed. Results showed that the expression level of miR-100 in HCC tissues was significantly lower than that in matched non-cancerous liver tissues. Also, low-miR-100 expression was observed to be significantly correlated with higher tumor grade, higher incidence of lymph node metastasis, advanced TNM stage and higher incidence of tumor recurrence in HCC patients. Multivariate survival analyses suggested that low-miR-100 expression was an independent prognostic factor for HCC patients (HR = 1.66, 95 % CI 1.32-2.82, P = 0.019). In addition, we found that upregulation of miR-100 could inhibit growth and increase apoptosis of HCC cells by downregulating polo-like kinase 1 (plk1). In HCC tissues, miR-100 expression was inversely correlated with the expression of plk1 protein (r = -0.418; P = 0.029). Therefore, downregulation of miR-100 was correlated with progressive pathological feature and poor prognosis in HCC patients, and miR-100 could function as a tumor suppressor by targeting plk1. miR-100 may serve as a prognostic marker and molecular therapeutic target in HCC.

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