Long non-coding RNA ANRIL mitigates neonatal hypoxic-ischemic brain damage via targeting the miR-378b/ATG3 axis.

Hypoxic-ischemic brain injury (HIBD) is the most common form of brain injury in newborns and is a major burden on society. However, the molecular mechanism of HIBD remains unclear. Long non-coding RNA (lncRNA) has been demonstrated to be a key regulator in brain development and numerous neurological diseases. The present study identified the role and underlying mechanism of lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) in HIBD. The data indicated that ANRIL expression was significantly increased in hypoxia-stressed primary neurons and PC12 cells. Silencing ANRIL aggravated oxygen-glucose deprivation-induced cell injury. Mechanistically, microRNA (miR)-378b was predicted and confirmed as a direct target of ANRIL. A miR-378b inhibitor counteracted the effect of ANRIL on hypoxia-induced cell injury. Furthermore, ANRIL positively regulated autophagy related 3 (ATG3) expression and promoted autophagy through competitively binding to miR-378b. Overall, the present findings suggest that ANRIL exerts its protective effects via binding to miR-378b and upregulating ATG3 expression, suggesting the potential of ANRIL as a protective target for HIBD.

Assoication of XRCC1 gene polymorphisms with risk of non-small cell lung cancer.

DNA repair genes is a key factor for cancer susceptibility, and we conducted a case-control study to investigate the association of XRCC1 codons 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln) with risk of NSCLC. 210 NSCLC patients and 210 health control subjects were randomly selected from Huaihe Hospital between January 2012 and June 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to assess the genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln. By multivariate logistic regression analysis, we found individuals carrying with Trp/Trp and Arg/Trp + Trp/Trp genotypes were associated with a significantly increased risk of NSCLC compared with Arg/Arg genotype, and the OR (95% CI) were 3.15 (1.32-8.09) and 1.52 (1.02-2.28), respectively. The potential association of Arg/Trp+ Trp/Trp genotype of XRCC1 Arg194Trp with the risk of NSCLC is more evidence in smokers, and the OR (95% CI) was 1.78 (1.01-3.24). In conclusion, we found that XRCC1 Arg194Trp polymorphism may be associated with NSCLC risk, especially in smokers.

The implications and mechanisms of the extra-nuclear nucleolin in the esophageal squamous cell carcinomas.

In recent decades, the multi-functional protein nucleolin (NCL) has been reported to express outside the nucleus of many cancer cells. However, the expression and role of the extra-nuclear NCL in esophageal squamous cell carcinoma (ESCC) were not well characterized. Here, NCL was detected by immunohistochemistry and Western blotting in 60 ESCC tissues. Further, the associations of NCL, EGFR, CXCR4 and Ki67 were analyzed by in vitro assays. Our results showed that NCL expression in all 40 cases of ESCC tissues with metastasis was extensively located in the nucleus, cytoplasm and cell membrane (extra-nucleus), while NCL expression in all 20 cases of ESCC without metastasis was merely limited into the nucleus (intra-nucleus).The extra-nuclear NCL expression was positively correlated with the expression of EGFR, CXCR4 and Ki67 and serves as an independent prognostic factor for ESCC patients. In vitro, NCL siRNA (si-NCL) efficaciously affected the expression of EGF or SDF-1-induced p-AKT, p-ERK and Ki67. Also, NCL siRNA inhibited the capacity of migration and invasion of ECA109 cells. In conclusions, our study suggests that NCL is implicated in the initiation and transduction of EGFR and CXCR4 signaling and further up-regulates Ki67 expression to modulate the biological behaviors of ESCC. Clinically, the extra-nuclear NCL expression can be used as an important indicator to determine metastasis and predict the prognosis, which help develop new therapeutic strategies against ESCC.

Methylenetetrahydrofolate reductase 677TT genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis.

BACKGROUND: Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. MATERIAL/METHODS: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14-1.44; TT vs. CC: OR=1.67, 95% CI: 1.33-2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15-1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03-2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14-1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07-1.45). CONCLUSIONS: This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding.