Nanjing Medical University

About: Nanjing Medical University is a education organization based out in Nanjing, China. It is known for research contribution in the topics: Cancer & Cell growth. The organization has 52221 authors who have published 37904 publications receiving 635831 citations. The organization is also known as: National Jiangsu Medical College & Nanjing Medical College.

Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population

Abstract: // Chao Yang 1,* , Ran Tang 1,* , Xiang Ma 1,* , Younan Wang 1 , Dakui Luo 1 , Zekuan Xu 1 , Yi Zhu 1,2 and Li Yang 1 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, Nanjing, China * These authors have contributed equally to this work Correspondence to: Li Yang, email: // Keywords : gastric cancer, H19, polymorphism, genotype Received : November 17, 2014 Accepted : March 19, 2015 Published : April 15, 2015 Abstract Long non-coding RNA (lncRNA) H19 is involved in tumor development, progression, and metastasis. This case-control study assessed the association between H19 genetic variants and susceptibility to gastric cancer (GC) in a Chinese Han population. We genotyped four lncRNA H19 single nucleotide polymorphisms (SNPs) (rs217727 C > T, rs2839698 C > T, rs3741216 A > T, rs3741219 T > C) in 500 GC patients and 500 healthy controls. Carriers of variant rs217727T and rs2839698T alleles showed increased GC risk ( P = 0.008 and 0.011, respectively). Compared with the common genotype, CT + TT rs217727 and CT + TT rs2839698 genotypes were associated with significantly increased GC risk ( P = 0.040, adjusted odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.01–1.71; P = 0.033, adjusted OR = 1.31, 95% CI = 1.02–1.69, respectively). Further stratified analyses revealed that the association between GC risk and variant genotypes of rs217727 was more profound in younger individuals (≤59 years) and non-smokers, while the association between risk and the rare rs2839698 genotype persisted in men and rural subjects. rs2839698 CT and TT genotypes were also associated with higher serum H19 mRNA levels compared with the CC genotype. These findings suggest that lncRNA H19 SNPs may contribute to susceptibility to GC.

Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells

Abstract: Lung cancer is the leading cause of cancer death, and it is widely accepted that chronic inflammation is an important risk for the development of lung cancer. Now, it is recognized that the nucleotide-binding and oligomerization domain (NOD) like receptors (NLRs)-containing inflammasomes are involved in cancer-related inflammation. This study was designed to investigate the effects of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome on the proliferation and migration of lung adenocarcinoma cell line A549. Using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, scratch assay, and Transwell migration assay, we showed that activation of the NLRP3 inflammasome by LPS+ATP enhanced the proliferation and migration of A549 cells. Western blot analysis showed that activation of phosphorylation of Akt, ERK1/2, CREB and the expression of Snail increased, while the expression of E-cadherin decreased after the activation of NLRP3 inflammasome. Moreover, these effects were inhibited by the following treatments: i) downregulating the expression of NLRP3 by short hairpin RNA (shRNA) interference, ii) inhibiting the activation of NLRP3 inflammasome with a caspase-1 inhibitor, iii) blocking the interleukin-1β (IL-1β) and IL-18 signal transduction with IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP). Collectively, these results indicate that NLRP3 inflammasome plays a vital role in regulating the proliferation and migration of A549 cells and it might be a potential target for the treatment of lung cancer.

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Abstract: The histone H3K36 methyltransferase SETD2 is frequently mutated or deleted in a variety of human tumors. Nevertheless, the role of SETD2 loss in oncogenesis remains largely undefined. Here, we found that SETD2 counteracts Wnt signaling and its inactivation promotes intestinal tumorigenesis in mouse models of colorectal cancer (CRC). SETD2 was not required for intestinal homeostasis under steady state; however, upon irradiation, genetic inactivation of Setd2 in mouse intestinal epithelium facilitated the self-renewal of intestinal stem/progenitor cells as well as tissue regeneration. Furthermore, depletion of SETD2 enhanced the susceptibility to tumorigenesis in the context of dysregulated Wnt signaling. Mechanistic characterizations indicated that SETD2 downregulation affects the alternative splicing of a subset of genes implicated in tumorigenesis. Importantly, we uncovered that SETD2 ablation reduces intron retention of dishevelled segment polarity protein 2 (DVL2) pre-mRNA, which would otherwise be degraded by nonsense-mediated decay, thereby augmenting Wnt signaling. The signaling cascades mediated by SETD2 were further substantiated by a CRC patient cohort analysis. Together, our studies highlight SETD2 as an integral regulator of Wnt signaling through epigenetic regulation of RNA processing during tissue regeneration and tumorigenesis.

A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing

Abstract: Objective To report the feasibility of fetal chromosomal deletion/duplication detection using a novel bioinformatic method of low coverage whole genome sequencing of maternal plasma. Method Ap ractical methodFetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS), integrated with GC-bias correction, binary segmentation algorithm and dynamic threshold strategy, was developed to detect fetal chromosomal deletions/duplications of >10Mb by low coverage whole genome sequencing (about 0.08-fold). The sensitivity/specificity of the resultant FCAPS algorithm in detecting deletions/duplications was firstly assessed in silico and then tested in 1311 maternal plasma samples from those with known G-banding karyotyping results of the fetus. Results Deletions/duplications, ranged from 9.01 to 28.46Mb, were suspected in four of the 1311 samples, of which three were consistent with the results of fetal karyotyping. In one case, the suspected abnormality was not confirmed by karyotyping, representing a false positive case. No false negative case was observed in the remaining 1307 low-risk samples. The sensitivity and specificity for detection of >10-Mb chromosomal deletions/duplications were100% and 99.92%, respectively. Conclusion Our study demonstrated FCAPS has the potential to detect fetal large deletions/duplications (>10Mb) with low coverage maternal plasma DNA sequencing currently used for fetal aneuploidy detection. © 2013 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this article.

MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1).

Abstract: Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.