Genotypes of Papillary Thyroid Carcinoma With High Lateral Neck Metastasis in Chinese Population.

Papillary Thyroid Carcinoma (PTC) is one of the most commonly diagnosed cancer types in China, characterized by its early age at diagnosis and high 25-year survival rate. Distinct mutational patterns in PTC have been linked to activation of the mitogen-activated protein kinase (MAPK) signaling pathway. To explore the clinical significance of genomic variation patterns in Chinese patients with thyroid carcinoma, we investigated the genomic variants in 83 PTC cases with complete clinical records.

Characterization of genomic clones by targeted deep sequencing of ctDNA to monitor liver cancer.

Background: In recent years, the morbidity and mortality of cancer patients have continued to increase in China, and there is an urgent need to develop an effective method to monitor tumor dynamics and measure tumor burden. Derived from the cell-free fraction of blood in cancer patients, circulating tumor DNA (ctDNA) has been regarded as a promising surrogate for tumor tissue biopsies. With the development of sequencing technology, ctDNA has been recognized as a specific and highly sensitive biomarker, and it has become a hot research spot in recent years.

GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing.

Background: The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair.

Results: In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy.

Variations in Oral Microbiota Composition Are Associated With a Risk of Throat Cancer.

In this study, a next-generation sequencing strategy on 16 ribosomal RNA (16 rRNA) gene was employed to analyze 70 oral samples from 32 patients with throat cancer, nine patients with vocal cord polyp, and 29 healthy individuals (normal controls). Using this strategy, we demonstrated, for the first time, that the salivary microbiota of cancer patients were significantly different from those of patients with a polyp and healthy individuals. We observed that the beta diversity of the cancer group was divergent from both the normal and polyp groups, while alpha-diversity indices such as the Chao1 estimator ( = 8.

Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma.

Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes.

In vitro study of FUZ as a novel potential therapeutic target in non-small-cell lung cancer.

FUZ is regarded as a planar cell polarity effector that controls multiple cellular processes during vertebrate development. However, the role of FUZ in tumor biology remains poorly studied. Our purpose of this study is to discover the physiological effects and mechanism of FUZ in non-small-cell lung cancer (NSCLC) in vitro.

MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma.

ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux.

DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage.

Our previous study showed that knockdown the endogenous expression of DCUN1D3 (also called SCCRO3 or DCNL3) blocked the S phase progression after UV irradiation. Here, we show that the silence of DCUN1D3 can increase the cyclin-dependent kinase inhibitor p27 protein levels after UV irradiation. Through Co-immunoprecipitation experiments, we found that DCUN1D3 bound to CAND1.

The novel secretory protein CGREF1 inhibits the activation of AP-1 transcriptional activity and cell proliferation.

The transcription factor AP-1 plays an important role in inflammation and cell survival. Using a dual-luciferase reporter assay system and a library of 940 candidate human secretory protein cDNA clones, we identified that CGREF1 can inhibit the transcriptional activity of AP-1. We demonstrated that CGREF1 is secreted via the classical secretory pathway through the ER-to-Golgi apparatus.

PC3-secreted microprotein is a novel chemoattractant protein and functions as a high-affinity ligand for CC chemokine receptor 2.

PC3-secreted microprotein (PSMP) or microseminoprotein is a newly discovered secreted protein whose function is currently unknown. In this study, PSMP was found to possess chemotactic ability toward monocytes and lymphocytes, and its functional receptor was identified as CCR2B. PSMP was identified as a chemoattractant protein from a PBMC chemoattractant platform screen that we established.

Human TTC5, a novel tetratricopeptide repeat domain containing gene, activates p53 and inhibits AP-1 pathway.

The transcription factor p53 and AP-1 play an important role in cellular proliferation, transformation and death. In this study, we investigated the role of a novel human gene, TTC5 (tetratricopeptide repeat domain 5), in the regulation of cell signaling pathway and cell viability. TTC5 is a member of the TTC family of proteins and has previously been shown to participate in cellular stress response.

[Comparative analysis on both high risk behaviours, infection of HIV and syphilis between married and unmarried men who have sex with men].

Objective: To understand the distribution of marriage status among men who have sex with men (MSM) in the city of Changzhou, and to explore the impact of marriage on AIDS related high risk behaviors and HIV infection in this population.

Methods: Target sampling (snowball sampling) was adopted to carry out a cross-sectional study, and structured questionnaire-based interviews were conducted to collect information on social demography, HIV related high risk behaviors. Blood and urine samples were collected to detect HIV, syphilis, gonorrhea and Chlamydia trachomatis infections.

[Construction of recombinant NF-κB reporter adenovirus and activity analysis].

Objective: To study the feasibility of adenovirus-based nuclear factor-κB (NF-κB) reporter as a model to screen the upstream signal regulators of NF-κB.

Methods: A type 5 (E1/E3 deficient) adenovirus vector pAdxsi was used to construct the NF-κB reporter adenovirus. Multiple adherent and suspending cell lines were infected by the NF-κB reporter adenovirus, and the luciferase activity of the NF-κB reporter gene was measured.

Suppression of non-small cell lung cancer proliferation and tumorigenicity by DENND2D.

DENND2D was identified as being down-regulated in lung cancer using a lung cancer low-expression suppression subtractive hybridization (SSH) library. In this study, DENND2D down-regulation has been observed not only in non-small cell lung cancer (NSCLC) cell lines and lung squamous cell carcinoma (SCC) tissues, but also in immortalized human bronchial epithelial (IHBE) cell lines and precancerous lesions, indicating that the down-regulation of DENND2D may be an early event in lung cancer. The relative DNA copy number and mRNA and protein expression levels of DENND2D were determined in vitro, and they revealed a complicated regulatory network at the genomic, transcriptional and translational levels.

In vitro biological characterization of DCUN1D5 in DNA damage response.

Background: Novel prognostic biomarkers or therapeutic molecular targets for laryngeal squamous cell carcinoma (LSCC) are an urgent priority. We here sought to identify multiple novel LSCC-associated genes.

Methods: Using high-density microarray expression profiling, we identified multiple genes that were significantly altered between human LSCCs and paired normal tissues.

Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell growth by autophagy and apoptosis in vitro and in vivo.

TMEM166 is a novel programmed cell death-related molecule. In this report, we constructed a recombinant adenovirus 5-TMEM166 vector (Ad5-TMEM166) and evaluated its expression and anti-tumor activities in vitro and in vivo. Cell viability analysis revealed that the adenovirus-mediated increase of TMEM166 inhibited tumor cell growth in a dose- and time-dependent manner.

VSTM1-v2, a novel soluble glycoprotein, promotes the differentiation and activation of Th17 cells.

Cytokines are soluble proteins that mediate immune reactions and are responsible for communication among immune cells. CD4(+) T cells are the principle sources of cytokines of adaptive immunity. Cytokines play critical roles in the differentiation and effector function of CD4(+) T cells.

CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest.

Human transcriptional adaptor hADA2a is an important component of the general control nonderepressible 5 (GCN5) histone acetyltransferase complex. Here, we report that coiled-coil domain containing 134 (CCDC134), a novel nuclear protein, binds to hADA2a and enhances the stability of the hADA2a protein in unstressed conditions. Furthermore, CCDC134 was found to participate in the p300/CBP-associated factor (PCAF) complex via hADA2a and affect the histone acetyltransferase activity of the complex.

Human HS1BP3 induces cell apoptosis and activates AP-1.

In the present study, we characterized the function of HS1-binding protein 3 (HS1BP3), which is mutated in essential tremor and may be involved in lymphocyte activation. We found that HS1BP3 localized to the mitochondria and endoplasmic reticulum partially. Overexpression of HS1BP3 induced apoptosis in HEK293T and HeLa cell lines.

Identification of C1qTNF-related protein 4 as a potential cytokine that stimulates the STAT3 and NF-κB pathways and promotes cell survival in human cancer cells.

The NF-κB and IL6/STAT3 pathways are major participants in tumor-promoting inflammation. C1qTNF related protein (CTRP) is a family with multiple physiological functions, but their involvement in tumor-promoting inflammation has received little attention. For the first time, we have identified CTRP4 as a novel secretary protein by N-terminal sequencing.

[Study on the mechanism of C17orf62 induced cell death].

Objective: To isolate the long coding sequence of human novel gene C17orf62 which is named as C17orf62-L by us, and analyze its effects on cell viability, subcellular localization, and expression profile in multiple cell lines.

Methods: RT-PCR (reverse transcription polymerase chain reaction ) was used to clone C17orf62-L which encoded 187 amino acids from human multi-tissue cDNA library. We used bioinformatics analysis to identify structural characteristics of C17orf62-L, and RT-PCR to detect its expression.

Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1.

The c-Jun NH(2)-terminal kinase (JNK) signaling pathway participates in many physiological functions. In the current study we reported the cloning and characterization of five novel JNK2 transcript variants, which were designated as JNK2α3, JNK2α4, JNK2β3, JNK2γ1 and JNK2γ2, respectively. Among them, JNK2α4 and JNK2γ2 are potential non-coding RNA because they contain pre-mature stop codons.

Human SBK1 is dysregulated in multiple cancers and promotes survival of ovary cancer SK-OV-3 cells.

Protein kinases are involved in comprehensive cellular processes and also implicated in many human diseases. SH3-binding domain kinase 1 (SBK1) was first cloned and characterized in rat and the human cDNA was cloned in our lab in 2006, but the expression and function of endogenous protein have not been well studied in human. In this follow up study, we screened a panel of cell lines and tissues, as well as a tumor tissue array for SBK1 expression at both RNA and protein levels.

High-throughput screening identifies CHMP4A associated with hypoxia-inducible factor 1.

Aims: Tumor hypoxia is a common phenomenon and hypoxia-inducible factor-1 is the transcription factor that is most closely associated with hypoxia. Hypoxia-inducible factor-1 is overexpressed in most solid tumors and plays a vital role in hypoxic acclimatization, energy metabolism, tumor angiogenesis, tumor invasion, and drug tolerance in cancer cells. We aimed to identify novel human genes associated with the stability and transcriptional activity of hypoxia-inducible factor-1.

AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK pathway.

The transcription factor AP-1 plays an important role in cellular proliferation, transformation and death. In this study, we report a novel human gene, AC3-33 (GenBank name: c3orf33, FLJ31139), which encodes a secretory protein that can inhibit Elk1 transcriptional activity via ERK1/2 pathway. The AC3-33 mRNA encodes a protein of 251 amino acids, which is a classical secretory protein.