Polycomb proteins RING1A/B promote H2A monoubiquitination to regulate female gametophyte development in Arabidopsis.

A functional female gametophyte is the basis of successful sexual reproduction in flowering plants. During female gametophyte development, the megaspore mother cell (MMC), which differentiates from a single subepidermal somatic cell in the nucellus, undergoes meiosis to produce four megaspores; only the one at the chalazal end, referred to as the functional megaspore (FM), then undergoes three rounds of mitosis and develops into a mature embryo sac. Here, we report that RING1A and RING1B (RING1A/B), two functionally redundant Polycomb proteins in Arabidopsis, are critical for female gametophyte development. Mutations of RING1A/B resulted in defects in the specification of the MMC and the FM, and in the subsequent mitosis of the FM, thereby leading to aborted ovules. Detailed analysis revealed that several genes essential for female gametophyte development were ectopically expressed in the ring1a ring1b mutant, including Argonaute (AGO) family genes and critical transcription factors. Furthermore, RING1A/B bound to some of these genes to promote H2A monoubiquitination (H2Aub). Taken together, our study shows that RING1A/B promote H2Aub modification at key genes for female gametophyte development, suppressing their expression to ensure that the development progresses correctly.

Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine.

Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.

Bizarre parosteal osteochondromatous proliferation in the distal ulna where the lesion is continuous with the medullary cavity: a case report.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign bone tumor, it is also called "Nora's lesion". The lesion is characterized by heterotopic ossification of the normal bone cortex or parosteal bone. The etiology of BPOP is unclear and may be related to trauma. In most BPOPs, the lesion is not connected to the medullary cavity. Here we report an atypical case, characterized by reversed features compared to the typical BPOP, which demonstrated continuity of the lesion with the cavity. CASE PRESENTATION: An 11-year-old female child had a slow-growing mass on her right wrist for 8 months with forearm rotation dysfunction. Plain X-rays showed an irregular calcified mass on the right distal ulna, and computed tomography (CT) showed a pedunculated mass resembling a mushroom protruding into the soft tissue at the distal ulna. The medulla of this lesion is continuous with the medulla of the ulna. A surgical resection of the lesion, together with a portion of the ulnar bone cortex below the tumor was performed, and the final pathology confirmed BPOP. After the surgery, the child's forearm rotation function improved significantly, and there was no sign of a recurrence at 1-year follow-up. CONCLUSION: It is scarce for BPOP lesions to communicate with the medullary cavity. However, under-recognition of these rare cases may result in misdiagnosis or inappropriate treatment thereby increasing the risk of recurrence. Therefore, special cases where BPOP lesions are continuous with the medulla are even more important to be studied to understand better and master these lesions. Although BPOP is a benign tumor with no evidence of malignant transformation, the recurrence rate of surgical resection is high. We considered the possibility of this particular disease prior to surgery and performed a surgical resection with adequate safety margins. Regular postoperative follow-up is of utmost importance, without a doubt.

Improvement of thermostability by increasing rigidity in the finger regions and flexibility in the catalytic pocket area of Pseudoalteromonas porphyrae κ-carrageenase.

Poor thermostability reduces the industrial application value of κ-carrageenase. In this study, the PoPMuSiC algorithm combined with site-directed mutagenesis was applied to improve the thermostability of the alkaline κ-carrageenase from Pseudoalteromonas porphyrae. The mutant E154A with improved thermal stability was successfully obtained using this strategy after screening seven rationally designed mutants. Compared with the wild-type κ-carrageenase (WT), E154A improved the activity by 29.4% and the residual activity by 51.6% after treatment at 50 °C for 30 min. The melting temperature (Tm) values determined by circular dichroism were 66.4 °C and 64.6 °C for E154A and WT, respectively. Molecular dynamics simulation analysis of κ-carrageenase showed that the flexibility decreased within the finger regions (including F1, F2, F3, F5 and F6) and the flexibility improved in the catalytic pocket area of the mutant E154A. The catalytic tunnel dynamic simulation analysis revealed that E154A led to enlarged catalytic tunnel volume and increased rigidity of the enzyme-substrate complex. The increasing rigidity within the finger regions and more flexible catalytic pocket of P. porphyrae κ-carrageenase might be a significant factor for improvement of the thermostability of the mutant κ-carrageenase E154A. The proposed rational design strategy could be applied to improve the enzyme kinetic stability of other industrial enzymes. Moreover, the hydrolysates of κ-carrageenan digested by the mutant E154A demonstrated increased scavenging activities against hydroxyl (OH) radicals and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals compared with the undigested κ-carrageenan.

Novel mesothelin-targeted chimeric antigen receptor-modified UNKT cells are highly effective in inhibiting tumor progression.

The design of chimeric antigen receptors (CAR) significantly enhances the antitumor efficacy of T cells. Although some CAR-T products have been approved by FDA in treating hematological tumors, adoptive immune therapy still faces many difficulties and challenges in the treatment of solid tumors. In this study, we reported a new strategy to treat solid tumors using a natural killer-like T (NKT) cell line which showed strong cytotoxicity to lyse 15 cancer cell lines, safe to normal cells and had low or no Graft-versus-host activity. We thus named it as universal NKT (UNKT). In both direct and indirect 3D tumor-like organ model, UNKT showed efficient tumor-killing properties, indicating that it could penetrate the microenvironment of solid tumors. In mesothelin (MSLN)-positive tumor cells (SKOV-3 and MCF-7), MSLN targeting CAR modified-UNKT cells had enhanced killing potential against MSLN positive ovarian cancer compared with the wild type UNKT, as well as MSLN-CAR-T cells. Compared with CAR-T, Single-cell microarray 32-plex proteomics revealed CAR-UNKT cells express more effector cytokines, such as perforin and granzyme B, and less interleukin-6 after activation. Moreover, our CAR-UNKT cells featured in more multifunctionality than CAR-T cells. CAR-UNKT cells also demonstrated strong antitumor activity in mouse models of ovarian cancer, with the ability to migrate and infiltrate the tumor without inducing immune memory. The fast-in and -out, enhanced and prolonged tumor killing properties of CAR-UNKT suggested a novel cure option of cellular immunotherapy in the treatment of MSLN-positive solid tumors.

Expression characterization and cross-species complementation uncover the functional conservation of YABBY genes for leaf abaxial polarity and carpel polarity establishment in Saccharum spontaneum.

BACKGROUND: Cell polarity establishment and maintenance is indispensable for plant growth and development. In plants, the YABBY transcription factor family has a distinct role in leaf asymmetric polarity establishment and lateral organ initiation. However, for the important sugar crop Saccharum, little information on YABBY genes is available. RESULTS: In this study, a total of 20 sequences for 7 SsYABBY genes were identified in the sugarcane genome, designated as SsYABBY1-7 based on their chromosome locations, and characterized by phylogenetic analysis. We provided a high-resolution map of SsYABBYs' global expression dynamics during vegetative and reproductive organ morphogenesis and revealed that SsYABBY3/4/5 are predominately expressed at the seedling stage of stem and leaf basal zone; SsYABBY2/5/7 are highly expressed in ovules. Besides, cross-species overexpression and/or complementation verified the conserved function of SsYABBY2 in establishing leaf adaxial-abaxial polarity and ovules development. We found that the SsYABBY2 could successfully rescue the leaves curling, carpel dehiscence, and ovule abortion defects in Arabidopsis crc mutant. CONCLUSIONS: Collectively, our study demonstrates that SsYABBY genes retained a conserved function in establishing and preserving leaf adaxial-abaxial polarity and lateral organ development during evolution.

Characterization of a bifunctional and endolytic alginate lyase from Microbulbifer sp. ALW1 and its application in alginate oligosaccharides production from Laminaria japonica.

The diverse biological activities of alginate oligosaccharides attracted extensive exploration of alginate lyases with various substrate specificity and enzymatic properties. In this study, an alginate lyase from Microbulbifer sp. ALW1, namely AlgL7, was phylogenetically classified into the polysaccharide lyase family 7 (PL7). The conserved amino acid residues Tyr606 and His499 in AlgL7 were predicted to act as the general acid/base catalysts. The enzyme was enzymatically characterized after heterologous expression and purification in E. coli. AlgL7 displayed optimal activity at 40 °C and pH 7.0. It had good stability at temperature below 35 °C and within a pH range of 5.0-10.0. AlgL7 exhibited good stability against the reducing reagent ß-ME and the surfactants of Tween-20 and Triton X-100. The degradation profiles of alginate indicated AlgL7 was a bifunctional endolytic alginate lyase generating alginate oligosaccharides with the degrees of polymerization 2-4. The degradation products of sodium alginate exhibited stronger antioxidant activities than the untreated polysaccharide. In addition, AlgL7 could directly digest Laminaria japonica to produce alginate oligosaccharides. These characteristics of AlgL7 offer a great potential of its application in high-value utilization of brown algae resources.

Rapid degradation of p-arsanilic acid and simultaneous removal of the released arsenic species by Co-Fe@C activated peroxydisulfate process.

In this study, a bimetallic composite catalyst (Co-Fe@C) was fabricated with calcination at high temperature (800 °C) by using Co-MIL-101 (Fe) as the precursor. The characterization results showed that the resulted Co-Fe@C composite mainly consisted of carbon, FeCo alloys, Fe3O4, Co3O4 and FeO, and owned evident magnetism. In addition, the Co-Fe@C was employed to activate the peroxydisulfate (PDS) to degrade a representative organic pollutant (p-arsanilic acid, p-ASA) and the main factors were optimized, which involved 0.2 g L-1 of catalyst dosage, 1.0 g L-1 of PDS dosage and 5.0 of initial pH. Under the optimal condition, Co-Fe@C/PDS system could completely degrade p-ASA (20 mg L-1) in 5 min. In the Co-Fe@C/PDS system, SO4-·, Fe(IV) and ·OH were the main species during p-ASA degradation. Under the attack of these species, p-ASA was first decomposed into phenols and then transformed into the organics acids and finally mineralized into CO2 and H2O through a series of reactions like hydroxylation, dearsenification, deamination and benzene ring opening. Importantly, most of the released inorganic arsenic species (93.40%) could be efficiently adsorbed by the catalyst.

A preliminary study of buccal and lingual alveolar bone thickness of posterior teeth in patients with skeletal Class III malocclusion and mandibular asymmetry.

INTRODUCTION: The purposes of this retrospective study were to investigate the buccal and lingual alveolar bone thickness values of the posterior teeth in patients with asymmetrical skeletal Class III malocclusion and compare them with patients with symmetrical skeletal Class III and Class I malocclusion. METHODS: Seventy-eight cone-beam computed tomography scans were classified into 3 groups according to the sagittal pattern and menton deviation: asymmetrical Class III (n = 26), symmetrical Class III (n = 26), and symmetrical Class I (n = 26). The buccal and lingual alveolar bone thickness of the first molar and premolars in the maxilla and mandible were measured at 3, 6, and 8 mm apical to the cementoenamel junction and the apical and middle levels of the root. Measurements were compared among the 3 groups. RESULTS: In the asymmetrical Class III group, the buccal alveolar bone along the distobuccal root of the maxillary first molar on the deviated side was thinner by 1.07 to 1.10 mm than that in the symmetrical Class I group at 6-mm, 8-mm, and middle-level planes (P <0.001, P <0.01, and P <0.001). The buccal alveolar bone thickness along the distal and mesial roots of the mandibular first molar on the deviated side was thinner by 1.28 to 1.85 mm, and by 0.72 to 1.21 mm, respectively (P <0.001 and P <0.01), than that in the symmetrical Class I group at 6-mm, 8-mm, apical and middle-level planes. CONCLUSIONS: In this preliminary study, patients with skeletal Class III malocclusion showed thinner buccal and lingual alveolar bone in the posterior teeth than subjects with Class I malocclusion. Particular attention should be paid to buccal alveolar bone thickness along the distobuccal root of the maxillary and distal root of the mandibular first molar to prevent periodontal complications in decompensation. Future studies should involve larger sample sizes, more repeatable and comprehensive measuring and statistical methods.

ATP binding cassette transporters ABCG1 and ABCG16 affect reproductive development via auxin signalling in Arabidopsis.

Angiosperm reproductive development is a complex event that includes floral organ development, male and female gametophyte formation and interaction between the male and female reproductive organs for successful fertilization. Previous studies have revealed the redundant function of ATP binding cassette subfamily G (ABCG) transporters ABCG1 and ABCG16 in pollen development, but whether they are involved in other reproductive processes is unknown. Here we show that ABCG1 and ABCG16 were not only expressed in anthers and stamen filaments but also enriched in pistil tissues, including the stigma, style, transmitting tract and ovule. We further demonstrated that pistil-expressed ABCG1 and ABCG16 promoted rapid pollen tube growth through their effects on auxin distribution and auxin flow in the pistil. Moreover, disrupted auxin homeostasis in stamen filaments was associated with defective filament elongation. Our work reveals the key functions of ABCG1 and ABCG16 in reproductive development and provides clues for identifying ABCG1 and ABCG16 substrates in Arabidopsis.

ROC Curve Analysis of the Sensitivity and Specificity of Biochemical Detection of Intrahepatic Cholestasis during Pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy outcomes in mothers and infants. The aim was to evaluate the sensitivity and specificity of biochemical detection of ICP by ROC curve and to determine the threshold of more reliable experimental indicators. MATERIALS AND METHODS: 305 patients and 305 healthy pregnant women were enrolled in the study. RESULTS: The average levels of TBA, ALT, and AST in the ICP group were much higher than those in the control group (P<0. 001); the area of both CG and TBA under ROC curve was up to 0.99, the sensitivity was 97.7%, and the specificity was 99.3%. CONCLUSIONS: This study did not find any single specificity and sensitivity markers that could be used to reliably diagnose ICP. In the future, we will pay more attention to the correlation between sensitive biochemical indicators and adverse pregnancy outcomes.

Analysis of salivary exosomal proteins in young adults with severe periodontitis.

OBJECTIVES: Salivary exosomes harbour numerous constituents associated with oral and systemic diseases. However, no reports addressed components of salivary exosomes in patients with periodontitis. Our study aims to explore salivary exosomal proteins in young adults with severe periodontitis (SP) and to analyse the relationships between different proteins. MATERIALS AND METHODS: We collected saliva from 11 young adults with SP and 11 periodontally healthy subjects. After isolation of salivary exosomes, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse proteins. Gene ontology analysis was performed based on GeneCodis, and interaction network analysis for unique salivary exosomal proteins was performed by STRING. RESULTS: Twenty-six proteins were identified only in the SP group, and 58 proteins were identified only in the healthy group. Gene ontology analysis revealed that innate immune response, cytolysis and complement activation were highly enriched in the SP group. Interaction network analysis showed that the correlations among immune-related proteins (e.g. complement components and chemokine (C-C motif) ligand 28) were significant in the SP group. C6 proteins expressed only in the SP group were evaluated by Western blotting. CONCLUSIONS: Salivary exosomes from periodontitis patients are enriched immune-related proteins that might participate in the immune response during the development of periodontitis.

Assessment of buccal and lingual alveolar bone thickness and buccolingual inclination of maxillary posterior teeth in patients with severe skeletal Class III malocclusion with mandibular asymmetry.

INTRODUCTION: The purpose of this study was to evaluate the buccal and lingual alveolar bone thickness and buccolingual inclination of maxillary posterior teeth in patients with severe skeletal Class III malocclusion with and without mandibular asymmetry and compare with those in patients with skeletal Class I malocclusion. METHODS: Cone-beam computed tomography images of 69 patients with severe skeletal Class III malocclusion and 30 patients with skeletal Class I malocclusion were collected and reconstructed with Dolphin 3D software. Based on the distance from menton to the sagittal plane (d), the patients with skeletal Class III malocclusion were divided into a symmetry group (d ≤ 2 mm) and an asymmetry group (d ≥ 4 mm). Buccal and lingual alveolar bone thickness and buccolingual inclination of maxillary posterior teeth were measured and compared. Correlations among dental measurements, severity of sagittal discrepancy, and mandibular deviation were analyzed. RESULTS: Maxillary posterior teeth on the deviated side in Class III asymmetry group and symmetry group were buccally inclined compared with the Class I group (P < 0.001). A significant negative correlation was noted between buccolingual inclination of maxillary posterior teeth and ANB value with Spearman correlation coefficient of maxillary first molar, second premolar, and first premolar of -0.687, -0.485 and -0.506, respectively (P < 0.001). Maxillary first molar showed thinner buccal alveolar bone on deviated side in asymmetry group and symmetry group of Class III, compared with the Class I group, with average values of 1.21 mm, 1.19 mm, and 1.83 mm, respectively (P < 0.05). The maxillary first premolar also showed thinner buccal alveolar bone on deviated side in Class III asymmetry group compared with the Class I group, with average values of 0.87 mm and 1.28 mm, respectively (P < 0.05). CONCLUSIONS: Decompensation of buccally inclined posterior teeth in patients with skeletal Class III malocclusion should be more cautious owing to thinner buccal alveolar bone to avoid a high risk of fenestration and dehiscence.

Preliminary comparison of three-dimensional reconstructed palatal morphology in subjects with different sagittal and vertical patterns.

BACKGROUND: The aim of this study was to assess the difference of palatal morphology in different vertical patterns between skeletal Class I subjects and skeletal Class II subjects with retrusive mandible. METHODS: Seventy-six skeletal Class II subjects with retrusive mandible (38 females, 38 males) and 85 skeletal Class I subjects (45 females, 40 males) were collected retrospectively and divided into hyperdivergent, normodivergent and hypodivergent groups. CBCT images of these subjects were reoriented by Dolphin 3D Imaging software. Three-dimensional (3D) maxilla was segmented by ProPlan software before using Geomagic Studio software to reconstruct 3D palatal morphology. Deviation patterns on 3D colored map analysis was performed to compare the difference of 3D palatal morphology between different groups. RESULTS: 3D colored map analysis showed that male's palate was higher and wider than that of female in the posterior part, regardless of different sagittal and vertical patterns. In skeletal Class II subjects with retrusive mandible, males with hyperdivergent and normodivergent showed higher and narrower in the posterior part of palate, while females with hyperdivergent and normodivergent had a higher but no obviously narrow palate compared with the hypodivergent subjects. Skeletal Class II subjects with retrusive mandible showed flatter and narrower in the posterior part of palate than that of skeletal Class I subjects. CONCLUSIONS: Sagittal and vertical patterns have great influence on the palatal morphology and as the vertical dimension increased, the palate tended to be higher and narrower.

Genome-Wide Analysis of the YABBY Transcription Factor Family in Pineapple and Functional Identification of AcYABBY4 Involvement in Salt Stress.

The plant-specific transcription factor gene family, YABBY, belongs to the subfamily of zinc finger protein superfamily and plays an essential regulatory role in lateral organ development. In this study, nine YABBY genes were identified in the pineapple genome. Seven of them were located on seven different chromosomes and the remaining two were located on scaffold 1235. Through protein structure prediction and protein multiple sequence alignment, we found that AcYABBY3, AcYABBY5 and AcYABBY7 lack a C2 structure in their N-terminal C2C2 zinc finger protein structure. Analysis of the cis-acting element indicated that all the seven pineapple YABBY genes contain multiple MYB and MYC elements. Further, the expression patterns analysis using the RNA-seq data of different pineapple tissues indicated that different AcYABBYs are preferentially expressed in various tissues. RT-qPCR showed that the expression of AcYABBY2, AcYABBY3, AcYABBY6 and AcYABBY7 were highly sensitive to abiotic stresses. Subcellular localization in pineapple protoplasts, tobacco leaves and Arabidopsis roots showed that all the seven pineapple YABBY proteins were nucleus localized. Overexpression of AcYABBY4 in Arabidopsis resulted in short root under NaCl treatment, indicating a negative regulatory role of AcYABBY4 in plant resistance to salt stress. This study provides valuable information for the classification of pineapple AcYABBY genes and established a basis for further research on the functions of AcYABBY proteins in plant development and environmental stress response.

miRNA-1290 Promotes Aggressiveness in Pancreatic Ductal Adenocarcinoma by Targeting IKK1.

BACKGROUND/AIMS: MicroRNAs (miRNAs) are a group of non-coding RNAs that play diverse roles in pancreatic carcinogenesis. In pancreatic ductal adenocarcinoma (PDAC), NF-kB is constitutively activated in most patients and is linked to a mutation in KRAS via IkB kinase complex 1 (IKK1, also known as IKKa). We investigated the link between PDAC aggressiveness and miR-1290. METHODS: We used miRCURYTM LNA Array and in situ hybridization to investigate candidate miRNAs and validated the findings with PCR. The malignant behavior of cell lines was assessed with Cell Counting Kit-8, colony formation, and Transwell assays. A dual-luciferase reporter assay was used to evaluate the interaction between miR-1290 and IKK1. Protein expression was observed by western blotting. RESULTS: In this study, 36 miRNAs were dysregulated in high-grade pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues compared with low-grade PanIN tissues. The area under the curve values of miR-1290 and miR-31-5p were 0.829 and 0.848, respectively (95% confidence interval, 0.722-0.936 and 0.749-0.948, both P < 0.001). There was a significant correlation between miR-1290 and histological differentiation (P = 0.029), pT stage (P = 0.006), and lymph node metastasis (P = 0.001). In addition, the in vitro work showed that miR-1290 promoted PDAC cell proliferation, invasion, and migration. Western blotting and the dual-luciferase reporter assay showed that miR-1290 promoted cancer aggressiveness by directly targeting IKK1. The synergist effect of miR-1290 on the proliferation and metastasis of PDAC cells was attenuated and enhanced by IKK1 overexpression and knockdown, respectively. Consistent with the in vitro results, a subcutaneous tumor mouse model showed that miR-1290 functioned as a potent promoter of PDAC in vivo. CONCLUSION: MiR-1290 may act as an oncogene by directly targeting the 3'-untranslated region of IKK1, and the miR-1290/IKK1 pathway may prove to be a novel diagnostic and therapeutic target for PDAC.

Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy.

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.

Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression.

Association between FTO gene polymorphism (rs9939609 T/A) and cancer risk: a meta-analysis.

Obesity is a risk factor of cancer. Several genes have been found to play an important role in aetiology of obesity and tumourigenesis. Recently, some studies suggested that rs9939609 polymorphism might be significantly associated with cancer risk, while the results of some other studies were controversial. Databases with time limitation from January 1984 to April 2015 were searched. The pooled odds ratio (OR) with 95% confidence interval was calculated to assess the associations, and subgroup meta-analyses were performed according to the type of cancer and ethnicity of the study populations. Overall, the significant association between rs9939609 polymorphism and cancer risk was found in homozygote model and recessive model. As to subgroup classified by cancer type, there was significant association in endometrial cancer and pancreatic cancer, while no statistical significance was detected in other kind of cancers. Besides, in the subgroup analysis of ethnicity, our results indicated that rs9939609 polymorphism was significantly associated with cancer risk in Asians. The rs9939609 polymorphism may be involved the susceptibility of endometrial cancer and pancreatic cancer, especially in Asian populations. Thus, rs9939609 may be a potential biomarker in early diagnosis or gene therapy target of endometrial cancer and pancreatic cancer.