Biological significance of long non-coding RNA FTX expression in human colorectal cancer.

The purpose of this study was to determine the expression of long non-coding RNA (lncRNA) FTX and analyze its prognostic and biological significance in colorectal cancer (CRC). A quantitative reverse transcription PCR was performed to detect the expression of long non-coding RNA FTX in 35 pairs of colorectal cancer and corresponding noncancerous tissues. The expression of long non-coding RNA FTX was detected in 187 colorectal cancer tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of Long Non-coding RNA FTX expression. The effects of long non-coding RNA FTX expression on malignant phenotypes of colorectal cancer cells and its possible biological significances were further determined. Long non-coding RNA FTX was significantly upregulated in colorectal cancer tissues, and low long non-coding RNA FTX expression was significantly correlated with differentiation grade, lymph vascular invasion, and clinical stage. Patients with high long non-coding RNA FTX showed poorer overall survival than those with low long non-coding RNA FTX. Multivariate analyses indicated that status of long non-coding RNA FTX was an independent prognostic factor for patients. Functional analyses showed that upregulation of long non-coding RNA FTX significantly promoted growth, migration, invasion, and increased colony formation in colorectal cancer cells. Therefore, long non-coding RNA FTX may be a potential biomarker for predicting the survival of colorectal cancer patients and might be a molecular target for treatment of human colorectal cancer.

Simultaneous idiopathic segmental infarction of the great omentum with spontaneous splenic rupture: a rare association.

Idiopathic segmental infraction of the greater omentum (ISIGO) is a rare cause of acute abdomen. One of the main symptoms is right-side abdominal pain, while its etiology is still unclear. Until now, ISIGO simultaneously with spontaneous splenic rupture (SSR) has not been reported. Here, we presented a case of a 35-year old man, who was admitted with an acute abdomen, and the clinical diagnosis was ISIGO with SSR. He had a significant previous medical history of the vein thrombosis of lower limbs. Partial omental resection and splenectomy were performed, and the postoperative recovery of the patient was excellent. We also highlighted several possible theories to explain the etiology of the ISIGO, and emphasized that surgical methods, including laparoscopic surgery and laparotomy, are still the best way to treat the ISIGO at the emergency condition.

Prognostic role of YB-1 expression in breast cancer: a meta-analysis.

OBJECTIVE: In published studies, Y-box binding protein-1 (YB-1) correlated with the prognosis of patients with breast cancer (BC), but the specific role of YB-1 is still unclear. Our study aimed to evaluate the prognostic value of YB-1 in BC patients using meta-analysis based on the published studies. METHODS: We searched the relevant literatures deadline for June 2014 in databases, including PubMed, Embase, Medline and Cochrane library, and finally 8 studies were included in our study. Our study contained 1094 BC patients with 398 YB-1 positive and 696 YB-1 negative. RESULTS: Our results showed that YB-1 abnormal expression did not correlated with the lymph node status [OR = 1.258, 95% CI = 0.895-1.769, P = 0.186], high histological grade [OR = 2.709, 95% CI = 0.861-8.530, P = 0.089], histological type [OR = 0.837, 95% CI = 0.526-1.331, P = 0.452], P53 status [OR = 2.006, 95% CI 0.686-5.865, P = 0.203] and PR [OR = 0.607, 95% CI = 0.347-1.061, P = 0.080] in BC patients. But YB-1 over-expression was associated with other unfavorable factors: ER negativity [OR = 0.604, 95% CI = 0.388-0.941, P = 0.026], HER2 positivity [OR = 3.841, 95% CI = 2.637-5.594, P = 0.000], and high tumorous T stage [OR = 2.169, 95% CI = 1.295-3.632, P = 0.003]. In addition, our data suggested that high YB-1 expression had an adverse impact on 5-year OS [RR = 2.767, 95% CI = 2.054-3.727, P = 0.000] in BC patients. CONCLUSIONS: Our findings implied that YB-1 might a novel biomarker to predict the prognosis of BC, and could be a potential direction for developing diagnostic and therapeutic approaches in BC.

Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells.

BACKGROUND: Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. MATERIALS AND METHODS: EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. RESULTS: After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. CONCLUSIONS: Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment.

Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts (CAFs) in tumor stroma play an important role. Prostaglandin E2 (PGE2) and interleukin (IL)-6 signal pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA (miR)-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer (GC). miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition (EMT) and the stem-like properties of GC cells in a miR-149-IL-6-dependent manner. In addition to IL-6, PGE2 receptor 2 (PTGER2/EP2) was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 (COX-2)/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.

Prognostic significance of Beclin-1 expression in colorectal cancer: a meta-analysis.

OBJECTIVE: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. MATERIALS AND METHODS: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. RESULTS: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). CONCLUSIONS: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.

Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer.

Salinomycin is a novel identified cancer stem cells (CSCs) killer. Higher ALDH activity represents CSCs characterization. Here, we screened ALDH activities on several gastric cancer cell lines and divided them into ALDH(high) and ALDH(low) gastric cancer groups. ALDH(high) cancer cells (NCI-N87 and SNU-1) disclosed more CSCs characteristics, such as higher levels of Sox2, Nanog and Nestin, more floating spheroid bodies, more colony formation and more resistance to conventional chemotherapeutic drugs 5-Fu and CDDP, compared to these parameters observed in ALDH(low) cancer cells (P<0.01). Importantly, ALDH(high) cancer cells are relatively sensitive to salinomycin when compared to ALDH(low) cancer cells (P<0.01). Our results confirmed ALDH as functional marker of CSCs population on gastric cancer. Salinomycin might be selective therapy for CSCs fraction, which is resistant to conventional anticancer drugs 5-Fu and CDDP.

Protective effect of ambroxol against paraquat-induced pulmonary fibrosis in rats.

OBJECTIVE: To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat. METHODS: Adult male Sprague-Dawley rats (n=144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-ß1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed. RESULTS: In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-ß1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-ß1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis. CONCLUSION: The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.

Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa.

BACKGROUND AND AIM: Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line. METHODS: IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori-positive chronic gastritis patients or H. pylori-negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES-1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES-1 gastric mucosa cells. RESULTS: The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30%±13.17 versus 5.20%±6.31, respectively (P<0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES-1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly. CONCLUSIONS: This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.