Association of lncRNA SOX2OT rs9839776 polymorphism with gastric cancer risk in Korean: Case-control study.

Aberrant regulation of the long non-coding RNA SRY-box transcription factor 2 overlapping transcript (SOX2OT) has been reported in various diseases including gastric cancer (GC). However, an association between the well-studied rs9839776 single nucleotide polymorphism in SOX2OT and GC susceptibility has not been reported. This study aimed to evaluate the association between the rs9839776 single nucleotide polymorphism in SOX2OT and GC risk. Genotyping of rs9839776 was conducted using TaqMan genotyping assay for 460 patients with GC and 386 controls. We found that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased GC risk (P = .046, adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.52-1.00 and P = .044, AOR = 0.74, 95% CI = 0.56-0.99, respectively). In addition, stratified analysis revealed that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased risk of lymph node metastasis-negative (P = .039, AOR = 0.67, 95% CI = 0.46-0.98 and P = .049, AOR = 0.71, 95% CI = 0.51-1.00, respectively) and tumor stage I (A+B)/II (A+B+C) (P = .028, AOR = 0.66, 95% CI = 0.50-0.96 and P = .041, AOR = 0.71, 95% CI = 0.52-0.99, respectively) GC. Our findings suggest that the rs9839776 T allele may be a protective factor against GC susceptibility. Further research is needed to clarify whether rs9839776 affects SOX2OT expression.

Association of long noncoding RNA MALAT1 polymorphisms with gastric cancer risk in Korean individuals.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) drives tumorigenesis of various human cancers. However, the association between MALAT1 variants and gastric cancer (GC) risk is unknown. We performed a case-control study to evaluate the possible association between rs619586 and rs3200401 SNPs in MALAT and GC risk. METHODS: Samples from 458 patients with GC and 381 controls were genotyped using the TaqMan genotyping assay. RESULTS: In stratified analyses, we observed that rs3200401 CT in the codominant model and CT+TT in the dominant model were associated with increased GC risk in male patients (CT: odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.09-3.01, p = 0.022; CT+TT: OR = 1.74, 95% CI = 1.07-2.83, p = 0.026), and the differentiated (CT: OR =1.79, 95% CI = 1.18-2.73, p = 0.007; CT+TT: OR = 1.76, 95% CI = 1.17-2.64, p = 0.007), and intestinal (CT: OR = 1.67, 95% CI = 1.11-2.49, p = 0.013; CT+TT: OR = 1.68, 95% CI = 1.14-2.47, p = 0.009) GC subgroups. CONCLUSION: MALAT1 rs3200401 increases GC susceptibility and might affect GC development. Further studies are needed to validate our results in large populations and different ethnic groups.

Association Between lncRNA HULC rs7763881 Polymorphism and Gastric Cancer Risk.

PURPOSE: Gastric cancer (GC) is one of the most common cancers in the world. Recently, several studies have suggested that single-nucleotide polymorphisms (SNPs) of long noncoding RNA (lncRNA) are associated with GC risk. However, the association of the lncRNA highly upregulated in liver cancer (HULC) SNP with GC risk is not yet known. The aims of this study were to evaluate the association between HULC rs7763881 SNP and the risk of GC and GC subgroups via a case-control study. PATIENTS AND METHODS: rs7763881 was genotyped using TaqMan genotyping assay with 459 GC patients and 379 controls. RESULTS: A significant association between HULC rs7763881 SNP and GC risk was not found. However, after adjustment for age and gender, the rs7763881 recessive model (CC) showed a significant association with an increased GC risk in the undifferentiated (odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.17-2.94, P = 0.009), diffuse-type GC (OR = 1.72, 95% CI = 1.05-2.82, P = 0.033), LNM-positive (OR = 2.02, 95% CI = 1.24-3.27, P = 0.004), T3/T4 (OR = 1.75, 95% CI = 1.05-2.91, P = 0.032), and tumor stage III (OR = 2.01, 95% CI = 1.17-3.45, P = 0.011) subgroups when compared to the rs7763881 combined genotypes (AA+AC). Furthermore, after adjusting for age and gender, the rs7763881 additive model (CC) indicated a significantly higher GC risk than rs7763881 AA genotype in the undifferentiated (OR = 1.96, 95% CI = 1.15-3.32, P = 0.013), diffuse-type GC (OR = 2.08, 95% CI = 1.23-3.52, P = 0.004), and LNM-positive (OR = 2.00, 95% CI = 1.14-3.49, P = 0.016) subgroups. CONCLUSION: Our findings suggest that the HULC rs7763881 SNP is associated with increased susceptibility to GC. However, further studies are required to validate our results in large populations as well as different ethnic groups.

Correlations between Genetic Polymorphisms in Long Non-Coding RNA PRNCR1 and Gastric Cancer Risk in a Korean Population.

We evaluated the association between prostate cancer non-coding RNA 1 (PRNCR1) polymorphisms and the risk of developing gastric cancer (GC) and GC subgroups in Korea. A case-control study was conducted with 437 GC patients and 357 healthy controls using a TaqMan genotyping assay. A chi-squared test, binary logistic regression, and genetic models were used to explore the association between five PRNCR1 polymorphisms and GC risk. After adjusting for gender and age, overall analyses using the recessive model indicated that the rs13252298 GG genotype was significantly associated with increased risk of intestinal-type gastric cancer (IGC). In the stratification analyses, the recessive model indicated that the rs1016343 TT genotype was significantly associated with decreased GC risk in individuals aged <60 years showing lymph node metastasis (LNM)-negative results. The rs13252298 GG genotype in the recessive model showed increased GC risk in subjects aged ≥60 years showing LNM-positive results and those aged ≥60 years in tumor stage III. In the dominant model, the rs16901946 combined genotype (AG/GG) was significantly associated with increased GC risk in subjects aged <60 years with tumor stage III. In the recessive model, the rs16901946 GG genotype was associated with decreased risk of GC and IGC in males aged ≥60 years. Thus, genetic variations in PRNCR1 may contribute to susceptibility to GC.

Bogijetong decoction and its active herbal components protect the peripheral nerve from damage caused by taxol or nerve crush.

BACKGROUND: Bogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy. To understand the biological basis of BGJTD on protective effects against neuropathy, we investigated physiological and biochemical responses of the sciatic nerves deranged by taxol injection or crush injury in the rats. METHODS: Dissociated Schwann cells and neurons were prepared from the sciatic nerve and dorsal root ganglia (DRG) respectively and were treated with taxol and BGJTD. The sciatic nerve in the rat was injected with taxol or given crush injury. Animals were then administered orally with BGJTD. Effects of BGJTD treatment on cultured cells and in vivo sciatic nerves and DRG tissues were examined by immunofluorescence staining and western blot analysis. Sciatic nerve regeneration was assessed by histological observation using retrograde tracing technique and by behavioral hot plate test. Eighteen different herbal components of BGJTD were divided into 4 subgroups and were used to select herbal drugs that enhanced neurite outgrowth in cultured neurons. RESULTS: Morphological abnormalities in the sciatic nerve axons and DRG tissue caused by taxol injection were largely improved by BGJTD treatment. BGJTD treatment enhanced neurite outgrowth in cultured DRG neurons and improved Schwann cell survival. Phospho-Erk1/2 levels were elevated by BGJTD administration in the injured- or taxol-injected sciatic nerves. Vimentin phosphorylation catalyzed by cell division cycle 2 (Cdc2) kinase was induced from Schwann cells in the sciatic nerves after taxol injection and crush injury, and phospho-vimentin levels were further upregulated by BGJTD treatment. Retrograde tracing of DiI-labeled DRG sensory neurons revealed growth-promoting activity of BGJTD on axonal regeneration. A drug group (Be) composed of 4 active herbal components which were selected by neurite growth-enhancing activity was as effective as BGJDT for the recovery of thermal sensitivity of the hind paws which had been suppressed by taxol administration. CONCLUSIONS: These data suggest that BGJTD and its active herbal components may protects the peripheral nerve from damage caused by taxol injection and nerve crush.

Immune stimulatory effects of Loranthi ramulus on macrophages through the increase of NO and TNF-alpha.

The activation of macrophages by microorganisms plays an important role in host defense and immunopathology. Loranthi ramulus (LR) is commonly used as a traditional drug and health food in Korea. Here, we investigated the regulatory effects of LR on macrophage-mediated immune responses. Treatment of macrophages with LR resulted in the enhanced cell-surface expression of CD80, CD86 and major histocompatibility complex (MHC) class II, as well as the enhanced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha, and also iNOS and TNF-alpha mRNA expression. These alterations of LR-treated cells were associated with the activation of NF-kappaB and mitogen-activated protein kinases (MAPKs). LR increased the phosphorylation of MAPKs (JNK, ERK1/2, p38 MAPK) and the activation of NF-kappaB in Raw 264.7 cells. These results suggest that LR has increased NO and TNF-alpha production through phosphorylation of all three MAPKs following IkappaBalpha degradation and NF-kappaB activation. In conclusion, our results demonstrate that LR can effectively promote the activation of macrophages, suggesting that LR may possess the potential to regulate immune responses.

Toll-like receptor 4-mediated immunoregulation by the aqueous extract of Mori Fructus.

The aqueous extract of Mori Fructus (MF) exerts a change of phenotype and a cytoprotective effect in macrophages. The present study was carried out to investigate the immunomodulating activity of MF on the expression of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), co-stimulatory molecules and also interferon-gamma (IFN-gamma) in macrophages and splenocytes. Toll-like receptor 4 (TLR4) is a promising molecular target for immune-modulating drugs. It was hypothesized that one possible upstream signaling pathway leading to immunoregulation of MF may be mediated by TLRs. Multiple signaling molecules (NF-kappaB, ERK1/2, p38 and JNK) of the TLR4 signaling pathway were also detected. It was found that MF increased NO production and TNF-alpha secretion in RAW 264.7 and peritoneal macrophages, co-stimulatory molecules expression in peritoneal macrophages and IFN-gamma expression in splenocytes. Further studies indicated that MF could significantly induce the phosphorylation of signal molecules of MAPKs and the degradation of IkappaBalpha which finally led to the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB) for the target gene expression. All those notions disclosed that the aqueous extract MF is a new TLR4 activator, which induces a Th1 immune response as a consequence of induction of cytokines secretion, especially TNF-alpha and IFN-gamma.

ERK1/2-mediated Schwann cell proliferation in the regenerating sciatic nerve by treadmill training.

Proliferation of Schwann cells in the injured peripheral nerve supports axonal regeneration, and physical training in experimental animals has been shown to promote nerve regeneration. Extracellular signal-regulated kinase 1/2 (ERK1/2) activity can mediate neuronal responses to lesion signals, but its role in non-neuronal cells in the injured area is largely unknown. Here we report that treadmill training (TMT) facilitates axonal regeneration via the upregulation of phospho-ERK1/2 protein levels in Schwann cells in the injured sciatic nerve. Low-intensity, but not high-intensity, TMT increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation. TMT elevated levels of GAP-43 mRNA and protein, and phospho-ERK1/2 protein in the injured sciatic nerves. TMT also enhanced phospho-c-Jun protein levels in the injured nerve. In-vivo administration of the ERK1/2 inhibitor PD98059 eliminated phospho-c-Jun, suggesting ERK1/2 phosphorylation of the c-Jun protein. PD98059 treatment decreased levels of BrdU-labeled proliferating Schwann cells in the distal portion of the injured nerve, and delayed the axonal regrowth that was promoted by TMT. The present data suggest that increased ERK1/2 activity in Schwann cells may play an important role in TMT-mediated enhancement of axonal regeneration in the injured peripheral nerve.