LncRNA LINC02253 activates KRT18/MAPK/ERK pathway by mediating N6-methyladenosine modification of KRT18 mRNA in gastric cancer.

Long non-coding RNAs (lncRNAs) play a crucial role in gastric cancer (GC) progression. And understanding the role of N6-methyladenosine (m6A) in tumorigenesis is an emerging field in cancer research. Here, we identified a novel oncogene, lncRNA LINC02253, in GC. LINC02253 expression was found to be significantly increased in GC. And LINC02253 expression was closely correlated with tumor size, lymph node metastasis and TNM stage of GC. Besides, GC patients with higher LINC02253 expression had worse 5-year overall survival. Additionally, LINC02253 promoted GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, we determined that LINC02253 increased KRT18 expression through enhancing the stability of KRT18 mRNA. Furthermore, LINC02253 increased m6A modification of KRT18 mRNA to stabilize KRT18 mRNA by recruiting m6A writer METTL3. And, rescue experiments revealed that KRT18 mediated the effects of LINC02253 on growth, migration and invasion of GC cells through activating MAPK/ERK signaling pathway. In conclusion, we demonstrates that oncogenic lncRNA LINC02253 positively regulates GC growth and metastasis via increasing METTL3-mediated mRNA stability of KRT18, extending the understanding of GC pathogenesis regulated by lncRNAs.

Genetic association of PLCE1, C11orf92-C11orf93, and NOC3L with colorectal cancer risk in the Han population.

Colorectal cancer (CRC) is a common malignant tumor that is influenced by an interaction between genetic and environmental factors. Currently, the inherited factors of CRC are unclear. Our study selected 19 tag single nucleotide polymorphisms (tSNPs) to investigate whether they were associated with CRC in the Han population. In this Han Chinese case-control study, we genotyped 203 CRC cases and 296 controls using Sequenom MassARRAY technology and analyzed their associations with CRC using χ(2) tests, SNPStats software, and SHEsis software. Based on χ(2) tests, PLCE1 -rs2077218, rs11187877 (p = 0.049) and C11orf92-C11orf93-rs3802842 (p = 0.023) correlate with CRC risk. In the genetic model analyses, we found the genotype "CC" of rs3802842 in C11orf92-C11orf93 may significantly increase CRC risk in the recessive model (p = 0.0071), whereas "GT" of rs17109928 in NOC3L may decrease the risk in the over-dominant model (p = 0.0091). Using SHEsis software, we found PLCE1 and NOC3L are strongly linked, and the "GCCATTCTGTC" haplotype may increase the risk of CRC (p = 0.049). We found three genes (PLCE1, C11orf92-C11orf93, and NOC3L) are associated with CRC susceptibility. In combination with previous reports, our results suggest that these genes may be associated with CRC in the Han population.

LRP4 promotes migration and invasion of gastric cancer under the regulation of microRNA-140-5p.

BACKGROUND: Low-density lipoprotein receptor-related protein 4 (LRP4) has been reported to be implicated in multiple types of cancers. However, the significance of LRP4 in gastric cancer (GC) remains poorly elucidated. Therefore, it's urgent to investigate the importance and underlying mechanisms of LRP4 in GC. OBJECTIVE: To investigate the clinical roles of LRP4 in GC. METHODS: The LRP4 mRNA and miR-140-5p was measured by qRT-PCR. The protein expression was determined Western blot. Kaplan-Meier survival curves and Cox proportional hazard regression models were performed to evaluate prognosis. RESULTS: We demonstrated that LRP4 mRNA and protein was up-regulated in GC tissues for the first time. Its high expression was significantly correlated with malignant clinical features including TNM stage and lymph-node metastasis and poor prognosis for GC patients. LRP4 promotes migration, invasion and epithelial-mesenchymal transition (EMT) progress of GC cells. Mechanically, LRP4 regulated PI3K/AKT in GC cells. AKT inhibitors reversed the effects of LRP4. Finally, LRP4 was regulated by miR-140-5p in GC. CONCLUSIONS: Our findings showed that LRP4 has an important function in GC progression and promotes GC migration, invasion and EMT by regulating PI3K/AKT under regulation of miR-140-5p, providing a potential therapeutic target for GC.

Luteolin exerts an anticancer effect on gastric cancer cells through multiple signaling pathways and regulating miRNAs.

Accumulating studies confirmed that luteolin, a common dietary flavonoid which is widely distributed in plants and has diverse beneficial biological function, including anti-oxidant, anti-inflammation and anticancer properties. However, the detail mechanisms of luteolin on GC are poorly understood. Here, we investigated the anticancer effect of luteolin in GC cells in vitro and in vivo. Luteolin reduced the cell viability in a time and dose-dependent manner. Luteolin significantly inhibited cell cycle progress, colony formation, proliferation, migration, invasion and promoted apoptosis in vitro and in vivo. Luteolin also regulated these biological effects associated regulators. Mechanically, luteolin treatment regulated Notch1, PI3K, AKT, mTOR, ERK, STAT3 and P38 signaling pathways and modulated a series of miRNAs expression. These findings provide novel insight into the molecular function of luteolin which suggest its potential as a therapeutic agent for human GC.

MicroRNA-582 promotes tumorigenesis by targeting phosphatase and tensin homologue in colorectal cancer.

A number of studies have implicated that a class of non­coding RNAs named microRNAs (miRNAs or miRs) is associated with tumorigenesis and have identified miRNAs as promising targets for pharmaceutical intervention. Recently, the deregulated expression of miR­582 in tumor cells has been reported. However, the exact function of miR­582 in colorectal cancer (CRC) remains largely unknown. In thi study, we demonstrate that miR­582 is extensively upregulated in CRC tissues and cell lines. The overexpression of miR­582 significantly enhanced the proliferation and migration ability of the CRC cells. However, the use of a specific miR­582 inhibitor counteracted these effects. miR­582 may also play an oncogenic role by promoting tumor growth in vivo. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was identified as a putative target of miR­582; transfection of the cells with a lentivirus with miR­582 mimics substantially decreased both the mRNA and protein levels of PTEN. The restoration of PTEN expression in the CRC cells reversed the adverse effects of miR­582. Our findings therefore indicate that miR­582 promotes CRC progression by decreasing PTEN expression. These findings may also imply that miR­582 may be a target for therapeutic intervention in patients with CRC.

Genetic variants in TERT are associated with risk of gastric cancer in a Chinese Han population.

Telomerase reverse transcriptase (TERT) is a gene within the cancer susceptibility region located at Chr5p15.33, which is associated with multiple cancer types. In this study, we validated the association between TERT polymorphisms and gastric cancer (GC) risk with a case-control study in a Chinese Han population. A total of 302 GC patients and 300 control individuals were recruited. We identified three single nucleotide polymorphisms (SNPs) in TERT that were associated with GC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association. The minor alleles of three SNPs were associated with increased GC risk inallelic model analysis. For two of the SNPs, rs10069690 and rs2853676,, the dominant and additive model frequencies were higher in GC cases compared to controls. Further haplotype analysis revealed a protective effect of haplotype ''CG'' of the TERT gene, while the haplotype "TA" increased GC risk.Our resultsprovide new evidence for the association between TERT and GC susceptibility in the Chinese Han population.

[Efficacy comparison of laparoscopic versus open tension-free hernia repair using biologic mesh for inguinal strangulated hernia].

OBJECTIVE: To compare the efficacy of laparoscopic versus open tension-free mesh repair using biologic mesh for inguinal strangulated hernia. METHODS: Clinical data of 27 patients with inguinal strangulated hernia in the Shanxi Provincial People's Hospital between January 2012 and April 2014 were analyzed retrospectively. All the patients underwent one-stage tension-free repair using biological mesh, including laparoscopic(n=13) and open procedures(n=14). RESULTS: As compared with the open group, the laparoscopic group had shorter operative time [(90.8±11.6) min vs. (130.8±32.5) min, P<0.01], lower rates of hematoma/seroma and wound infection[(7.7% vs. 42.9%) and (0 vs. 28.6%) respectively, both P<0.05], faster recovery of bowel function [(2.5±0.3) d vs. (3.8±1.4) d, P<0.01], and shorter hospital stay [(6.3±1.8) d vs. (9.8±3.2) d, P<0.01]. The mean follow-up was 5.7 months (ranged from 2 to 12 months), and no recurrence or serious complications occurred. CONCLUSION: Laparoscopic tension-free hernia repair using biological mesh for inguinal strangulated hernia has significant advantage versus open operation.

Polymorphisms in the DUSP10 gene are associated with sex-specific colorectal cancer risk in a Han population.

AIMS AND BACKGROUND: Colorectal cancer (CRC) is common, especially in developed countries. CRC is a multifactorial disease influenced by both environmental and genetic factors. In this study, we investigated the role of genetic polymorphisms in the dual specificity protein phosphatase 10 (DUSP10) gene especially in sex-specific. METHODS: We selected nine DUSP10 tag single nucleotide polymorphisms (tSNPs) previously reported to be associated with colorectal cancer risk of in a case-control study from Xi'an city of China. RESULTS: In females, three SNPs were associated with decreased CRC risk: rs11118838, rs12724393, and rs908858. However, in males, only one SNP, rs908858, was associated with decreased CRC risk. Using a log-additive model, the rs11118838 "C" allele and the rs12724393 "G" allele were associated with decreased CRC risk in females, while the rs908858 "G" allele was associated with decreased CRC risk in both females and males. In addition, haplotype analysis also found "CG" and "CCT" were associated with the decreased CRC risk in females. CONCLUSIONS: Our findings suggest that DUSP10 polymorphisms influence the risk of developing CRC in Han Chinese and emphasize that sex should be considered in the design and analysis of health studies and biomedical research.

DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese population.

Dual-specificity protein phosphatases (DUSP) negatively regulate members of the mitogen-activated protein kinase superfamily, which is associated with cellular proliferation and differentiation. A recent study suggests that DUSP10 is frequently upregulated in colorectal cancer (CRC). Our study aimed to assess whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese by the χ²-test and the SHEsis software. We found that two tSNPs (rs908858, P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using the χ²-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629, rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype 'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ∼53%; the haplotype 'GCCCACCCA' may decrease the risk by ∼46%. Our results, combined with previous studies, suggest that certain mutations in DUSP10 correlate with the incidence of CRC. Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population.