MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.

These findings suggest that reactivated CD133 positive cells are frequently present in HCC. Additionally, increased CD133 expression corresponds with higher stage tumours in HCC, thus indicating a poor prognosis for patients. These data support the CSC hypothesis.

Orthotopic liver transplantation (OLT) is the only curative therapy of HCC with underlying cirrhosis, but due to HCC metastasis and recurrence, its benefit is limited to a small population who meet the strict selection criteria. We previously reported that Licartin ([ 131 I]mAb HAb18G/CD147) was safe and effective in treating HCC patients, and its antigen, HAb18G/ CD147, was closely related to HCC invasion and metastasis. Here, we reported a randomized controlled trial to assess the post-OLT antirecurrence efficacy of Licartin in advanced HCC patients. We randomized 60 post-OLT patients with HCC, who were at tumor stage 3/4 and outside the Milan criteria before OLT, into 2 groups. Three weeks after OLT, the treatment group received 15.4 MBq/kg of Licartin, while the control group received placebo intravenously for 3 times with an interval of 28 days. At 1-year follow-up, the recurrence rate significantly decreased by 30.4% (P ‫؍‬ 0.0174) and the survival rate increased by 20.6% (P ‫؍‬ 0.0289) in the treatment group, compared with those in the control group. For the control group versus the treatment group, the hazard ratio for recurrence H epatocellular carcinoma is the most common type of primary liver cancer and ranks sixth among cancers as a cause of death worldwide. 1 It is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent tumor recurrence. It has an annual incidence rate of 564,000 cases, and 55% of those are in China. 2 The mean natural survival time was reported to be only 3-6 months due to the rapid progression of tumor, especially the spread and metastasis. 3,4 Surgery is the preferred treatment, but less than 20% of patients have the chance to be treated surgically Abbreviations: AFP, alpha fetoprotein; CI, confidence interval; DBIL, direct bilirubin; mAb, monoclonal antibody; OLT, orthotopic liver transplantation; TNM, tumor-nodes-metastasis. From the

Chemotherapy is an important treatment modality for gastric cancer (GC); however, it usually fails because of drug resistance, especially multidrug resistance (MDR). Previously, we found a novel subset of MDR-associated microRNAs (miRNAs) through high-throughput functional screening. In this report, we investigated the exact roles and mechanisms of miR-23b-3p in the MDR of GC. Using gain or loss-of-function in in vitro and in vivo experiments, we found that overexpression of miR-23b-3p reversed cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumors to chemotherapy in vivo. Reporter gene assay and western blot analysis showed that ATG12 and HMGB2 were the direct targets of miR-23b-3p. Meanwhile, ATG12 and HMGB2 were positively associated with the occurrence of autophagy. Reducing the expression of these target genes by siRNA or inhibition of autophagy both sensitized GC cells to chemotherapy. These findings suggest that a miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop has a critical role in MDR in GC. In addition, miR-23b-3p could be used as a prognostic factor for overall survival in GC. In conclusion, our data demonstrated that miR-23b-3p inhibited autophagy mediated by ATG12 and HMGB2 and sensitized GC cells to chemotherapy, and suggested the potential application of miR-23b-3p in drug resistance prediction and treatment.

FTS could be safely applied in radical total gastrectomy to accelerate clinical recovery of gastric cancer patients.

MiR-296 might play important roles in the pathogenesis of esophageal cancer and considered as a potential target for this malignancy intervention.

Long noncoding RNAs (lncRNAs) have recently been identified to be involved in various diseases including cancer. NEAT1 is a recently identified lncRNA with its function largely unknown in human malignancy. In the present study, we investigated NEAT1 expression in 239 cases of clinical colorectal cancer specimens and matched normal tissues. Statistical methods were utilized to analyze the association of NEAT1 with clinical features, disease-free and overall survival of patients. Results showed that NEAT1 expression in colorectal cancer was up-regulated in 72.0% (172/239) cases compared with corresponding normal counterparts, and related to tumor differentiation, invasion, metastasis and TNM stage. Kaplan-Meier analysis proved that NEAT1 was associated with both disease-free survival and overall survival of patients with colorectal cancer that patients with high NEAT1 expression tend to have unfavorable outcome. Moreover, cox’s proportional hazards analysis showed that high NEAT1 expression was an independent prognostic marker of poor outcome. These results provided the first evidence that the expression of NEAT1 in colorectal cancer may play an oncogenic role in colorectal cancer differentiation, invasion and metastasis. It also proved that NEAT1 may serve as an indicator of tumor recurrence and prognosis of colorectal cancer.

SUMMARYAdenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modi®cation of pre-mRNA catalysed by an RNA-speci®c adenosine deaminase (ADAR). A-to-I RNA editing has been previously reported in the pre-mRNAs of brain glutamate and serotonin receptors and in lung tissue during in¯ammation. Here we report that systemic in¯ammation markedly induces inosinecontaining mRNA to approximately 5% of adenosine in total mRNA. Induction was the result of upregulation of A-to-I RNA editing as both dsRNA editing activity and ADAR1 expression were increased in the spleen, thymus and peripheral lymphocytes from endotoxin-treated mice. Upregulation of ADAR1 was con®rmed in vitro in T lymphocytes and macrophages stimulated with a variety of in¯ammatory mediators including tumour necrosis factor-a and interferon-g. A late induction of RNA editing was detected in concanavalin A-activated splenocytes stimulated with interleukin-2 in vitro. Taken together, these data suggest that a large number of inosine-containing mRNAs are produced during acute in¯ammation via up-regulation of ADAR1-mediated RNA editing. These events may affect the in¯ammatory and immune response through modulation of protein production.