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// Ting Sun 1, 2, * , Liang Ming 1, 2, * , Yunmeng Yan 1, 2, * , Yan Zhang 1, 2 and Haikuo Xue 1, 2 1 Key Clinical Laboratory of Henan Province, Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 2 Department of Medical Laboratory, Zhengzhou University, Zhengzhou 450001, China * These authors have contributed equally to the work Correspondence to: Liang Ming, email: mingliangzzu@163.com Keywords: aspirin, autophagy, Beclin 1, acetylation, colorectal cancer Received: May 19, 2017 Accepted: July 25, 2017 Published: August 19, 2017 ABSTRACT Regular use of aspirin can reduce cancer incidence, recurrence, metastasis and cancer-related mortality. Aspirin suppresses proliferation and induces apoptosis and autophagy in colorectal cancer cells, but the precise mechanism is not clear. In this study, we demonstrated that aspirin induced autophagosome formation in colorectal cancer cells, but autophagic degradation was blocked through aspirin-mediated Beclin 1 acetylation. Blocked autophagic degradation weakened aspirin-induced cell death. Collectively, our findings indicate the dual roles of aspirin on autophagy, and demonstrate a new mechanism by which Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells.

In mammals, methylation of the 5th position of cytosine (5mC) seems to be a major epigenetic modification of DNA. This process can be reversed (resulting in cytosine) with high efficiency by dioxygenases of the ten‐eleven translocation (TET) family, which perform oxidation of 5mC to 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine and 5‐carboxylcytosine. It has been demonstrated that these 5mC oxidation derivatives are in a dynamic state and have pivotal regulatory functions. Here, we comprehensively summarized the recent research progress in the understanding of the physiological functions of the TET proteins and their mechanisms of regulation of DNA methylation and transcription. Among the three TET genes, TET1 and TET2 expression levels have frequently been shown to be low in hepatocellular carcinoma (HCC) tissues and received most attention. The modulation of TET1 also correlates with microRNAs in a post‐transcriptional regulatory process. Additionally, recent studies revealed that global genomic 5hmC levels are down‐regulated in HCC tissues and cell lines. Combined with the reported results, identification of 5hmC signatures in HCC tissues and in circulating cell‐free DNA will certainly contribute to early detection and should help to design therapeutic strategies against HCC. 5hmC might also be a novel prognostic biomarker of HCC. Thus, a detailed understanding of the molecular mechanisms resulting in the premalignant and aggressive transformation of TET proteins and cells with 5hmC disruption might help to develop novel epigenetic therapies for HCC.

The aim is to investigate the changes in coagulation test results in subjects with varying serum levels of thyroid stimulating hormone.We performed a one-year retrospective analysis to retrieve combined results of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), D-dimer, free thyroxine (fT4), tri-iodothyronine (fT3), and thyroid stimulating hormone (TSH) from inpatients who were referred by general practitioners for routine blood testing. Cumulative results were retrieved for 2,794 such inpatients.Patients with a TSH level0.34 µIU/mL had higher PT values (10.43 ± 1.02 vs. 10.27 ± 0.91) and Fib values (3.00 ± 0.92 vs. 2.7 ± 0.56) compared with patients with 0.34 µIU/mLTSH5.6 µIU/mL. Conversely, the PT values (10.01 ± 0.95 vs. 10.27 ± 0.91) were lower and APTT (33.70 ± 4.17 vs. 32.56 ± 4.12) values higher in patients with TSH5.6 µIU/mL compared to patients with 0.34 µIU/mLTSH5.6 µIU/mL.There are changes in coagulation test results in subjects with varying levels of thyroid stimulating hormone.

BackgroundOxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice.MethodsRNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group.ResultsThe levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α(8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice.ConclusionThis study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.

To determine differences in levels of coagulation and superoxide dismutase in normal controls and type 2 diabetes mellitus patients with different stages of glucose control.Type 2 diabetes mellitus patients were divided into two groups according to their fasting blood glucose (GM1 and GM2) and HbA1c levels (BM1 and BM2). Blood clotting times and levels of serum superoxide dismutase were compared among the three groups. A receiver operating characteristic (ROC) curve was generated to evaluate predictors and determine their sensitivities and specificities. A Pearson correlation analysis was performed on the type 2 diabetes mellitus patients using standard methods to evaluate the association of serum levels of superoxide dismutase and coagulation parameters with certain disease risk factors. A multiple linear stepwise regression analysis was also performed.There is a significant difference in levels of superoxide dismutase (SOD) and activated partial thromboplastin time (APTT) between normal controls and type 2 diabetes patients with varying glucose tolerance statuses (Shorter APTT and increased SOD levels might be useful hemostatic markers in patients with type 2 diabetes mellitus.

Objectives Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality in the world. Accumulating evidence has highlighted the regulatory roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in HCC. Methods The lncRNA expression data and corresponding patient information were obtained from The Cancer Genome Atlas (TCGA) database. Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis was implemented using the Spearman correlation coefficient. Multivariate Cox regression survival analysis was utilized to extract prognostic lncRNAs in the network. Results Based on the “ceRNA hypothesis”, a global lncRNA-associated ceRNA network (LCeNET) in HCC was constructed. Nine lncRNAs were identified as hubs and found to be enriched in various cancer-related biological processes. In addition, ceRNA pairs associated with survival were screened to construct a lncRNA-miRNA-mRNA sub network. Finally, we developed a sixteen-lncRNA model that could classify patients into high- and low-risk subgroups with different survival outcomes, and MCM3AP-AS1 functioned as a hub in both LCeNET and prognostic model. Conclusions Our work will improve the understanding of lncRNA-mediated ceRNA regulatory mechanisms in HCC pathogenesis and facilitate the identification of candidate prognostic biomarkers for HCC.

Pancreatic cancer is one of the most lethal malignancies. Exosomes, which are released by multiple cell types, such as cancer cells, contain functional biomolecules (including proteins, nucleic acids and lipids) that can be horizontally delivered to recipient cells. Exosomes act as the most prominent mediator of intercellular communication and can regulate, instruct and re-educate their surrounding microenvironment and target specific organs. The present review performed an extensive search of multiple databases from 2005 to April 23 2017, for eligible literature relating to exosomes and their role in pancreatic cancer. With a focus on the latest findings for pancreatic cancer exosomes, their role in tumorigenesis was summarized, as well as their aggressive behaviors and their contribution to immunosuppression and therapy resistance in pancreatic cancer. In addition, the potential function of exosomes as novel diagnostic biomarkers is briefly discussed. Finally, we propose potential clinical applications for exosomes in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies. Exosomes, which are released by multiple cell types, such as cancer cells, contain functional biomolecules (including proteins, nucleic acids and lipids) that can be horizontally delivered to recipient cells. Exosomes act as the most prominent mediator of intercellular communication and can regulate, instruct and re-educate their surrounding microenvironment and target specific organs. The present review performed an extensive search of multiple databases from 2005 to April 23 2017, for eligible literature relating to exosomes and their role in pancreatic cancer. With a focus on the latest findings for pancreatic cancer exosomes, their role in tumorigenesis was summarized, as well as their aggressive behaviors and their contribution to immunosuppression and therapy resistance in pancreatic cancer. In addition, the potential function of exosomes as novel diagnostic biomarkers is briefly discussed. Finally, we propose potential clinical applications for exosomes in pancreatic cancer.

Objective: In order to summarize the role of exosomes in invasion and metastasis in gastric cancer (GC).Material: Exosomes are vesicles of endocytic origin ranging from 30 to 100 nm in size; they are composed of a lipid bilayer and contain DNA, mRNA, miRNA, circular RNA and multiple proteins. Recently, increasing evidence shows that exosomes play a crucial role in the tumorigenesis of GC.Results: In this review, we focus on the latest findings on GC exosomes, mainly summarizing their role in invasion and metastasis in GC. Then, exosomes? potential functions as novel diagnostic and therapeutic biomarkers for GC are briefly discussed. At last, we prospect the clinical application perspective of exosomes in GC.Conclusions: Exosomes play a vital role in gastric cancer carcinogenesis and metastasis.

Background Accumulating evidence suggested that the expression level of long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) was upregulated in various cancers, and high expression of SNHG1 was associated with metastasis and prognosis in patients with cancer.The relationship between SNHG1 expression and metastasis or prognosis in malignant tumors was investigated in this meta-analysis. Methods A systematic search was performed in PubMed, Web of Science, and Cochrane Library from inception until May 31, 2018. Hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of SNHG1 using Stata 12.0 software. Results A total of 10 studies including 1129 patients were finally enrolled in the meta-analysis based on the inclusion and exclusion criteria. Increased SNHG1 expression was significantly associated with lymph node metastasis (OR = 3.28, 95% CI = 2.02-5.33) and advanced TNM stage (OR = 0.26, 95% CI = 0.16-0.43). Moreover, high expression of SNHG1 could predict poor overall survival (HR = 2.32, 95% CI = 1.90-2.83), event-free survival (HR = 1.58, 95% CI = 1.06-2.35), recurrence-free survival (HR = 2.15, 95% CI = 1.23-3.77), progression-free survival (HR = 2.75, 95% CI = 1.70-4.46), and disease-free survival (HR = 1.93, 95% CI = 1.10-3.40) in patients with cancer. Conclusion The present meta-analysis demonstrated that upregulation of lncRNA SNHG1 might serve as a useful prognostic biomarker in various cancers.

Background MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored. Methodology/Principal Findings Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1. Conclusions/Significance Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.

The developmental stage-specific expression of the human β-like globin genes has been studied for decades, and many transcriptional factors as well as other important cis elements have been identified. However, little is known about the microRNAs that potentially regulate β-like globin gene expression directly or indirectly during erythropoiesis. In this study, we show that microRNA 23a (miR-23a) and miR-27a promote β-like globin gene expression in K562 cells and primary erythroid cells through targeting of the transcription factors KLF3 and SP1. Intriguingly, miR-23a and miR-27a further enhance the transcription of β-like globin genes through repression of KLF3 and SP1 binding to the β-like globin gene locus during erythroid differentiation. Moreover, KLF3 can bind to the promoter of the miR-23a∼27a∼24-2 cluster and suppress this microRNA cluster expression. Hence, a positive feedback loop comprised of KLF3 and miR-23a promotes the expression of β-like globin genes and the miR-23a∼27a∼24-2 cluster during erythropoiesis.

S-adenosylhomocysteine hydrolase (SAHH) is an enzyme, which catalyzes the hydrolysis of S-adenosylhomocysteine (SAH) which is formed after the donation of the methyl group of S-adenosylmethionine (SAM) to a methyl acceptor in methylation reaction. As a potent regulator of methylation, SAHH plays a critical role in methylation reaction in the cells. Here we cloned the SAHH gene from unicellular green alga Dunaliella salina (dsSAHH) and investigated its effects on flagellar regeneration of D. salina, and found that dsSAHH was upregulated both at the protein and the transcription levels during pH shock-triggered flagellar regeneration of D. salina. The flagellar regeneration was accelerated when dsSAHH was overexpressed, but it was inhibited by SAHH inhibitor 3-deazaadenosine (DZA). Moreover, a receptor for activated C kinase 1 from D. salina (dsRACK1), which was identified to interact with dsSAHH, was increased when dsSAHH was overexpressed in D. salina as shown by real-time PCR. The findings of this study suggest that dsSAHH may participate in the regulation of flagellar regeneration of D. salina.