Comprehensive analysis of long non-coding RNA-messenger RNA-microRNA co-expression network identifies cell cycle-related lncRNA in hepatocellular carcinoma
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Authors: Zhu, Hai-Rong; Yu, Xiang-Nan; Zhang, Guang-Cong; Shi, Xuan; Bilegsaikhan, Enkhnaran; Guo, Hong-Ying; Liu, Li-Li; Cai, Yu; Song, Guang-Qi; Liu, Tao-Tao; Dong, Ling; Janssen, Harry L. A.; Weng, Shu-Qiang; Wu, Jian; Shen, Xi-Zhong; Zhu, Ji-Min
Abstract
Long non-coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA-miRNA-mRNA co-expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor-free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor-free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA-mRNA-miRNA co-expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan-Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc-HACE1-6:1 and lnc-ICOSLG-11:1, are significantly upregulated in HCC tissues compared with adjacent tumor-free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.
PTPN2 rs1893217 single-nucleotide polymorphism is associated with risk of Behcet's disease in a Chinese Han population
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
Authors: Wu, Z.; Chen, H.; Sun, F.; Xu, J.; Zheng, W.; Li, P.; Chen, S.; Shen, M.; Zhang, W.; Li, M.; You, X.; Wu, Q.; Zhang, F.; Li, Y.
Abstract
Objective. Behcet's disease (BD) is a rare, chronic, relapsing, systemic, immune-mediated vasculitis and the etiology remains to be defined. This study investigated single-nucleotide polymorphisms (SNP) of tyrosine-protein phosphatase non-receptor type 2 (PTPN2) and inducible T-cell co-stimulator-ligand gene (ICOSLG) in Chinese Han BD patients and healthy controls because SNPs of these two genes are associated with risk of developing other auto-inflammation diseases. Methods. A total of 407 BD patients and 679 ethnically matched healthy controls were recruited for genotyping of PTPN2 rs1893217, rs2542151, rs2847297 and rs7234029 SNPs and ICOSLG rs2838519 and rs762421 SNPs using a Sequenom MassArray system. Results. PTPN2 rs1893217 was associated with risk of developing BD (chi(2)=10.01, p(c)=0.040), while the PTPN2 rs2542151 genotype had a weak association in basic genotype analysis (chi(2)=7.49, p=0.024), but it could not withstand the strongest Bonferroni correction (p=0.14). In contrast, PTPN2 rs2847297 and rs7234029 and ICOSLG rs2838519 and rs762421 did not correlate with BD risk. Moreover, logistic analysis with the additive, dominant and recessive genetic models did not reveal any statistical difference between BD cases and controls (p(c)>0.05). In addition, associations were observed between the two SNPs (rs1893217, rs2542151) and the patients with gastrointestinal involvement (p(c)=0.027, p(c)=0.032, respectively). Conclusion. PTPN2 variant rs1893217 was associated with risk of BD development in a Han Chinese population. Further study will confirm this finding and investigate the role of PTPN2 in development of BD.