Gastric cancer (GC) is a highly aggressive malignant tumor. Its high mortality rate prompts the urgent need for novel therapeutic agents. The aim of this study is to detect the expression of CRM1 in GC, which has not been reported to date. The expression of CRM1 in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 120 GC patients was measured by immunohistochemistry. In addition, correlations between the CRM1 staining and the clinicopathologic features as well as survival were analyzed. Positive expression rates of CRM1 in GC and ANCT were 57.8 and 6.7%, respectively. High expression of CRM1 was significantly associated with increased serum level of carcinoma embryonic antigen (CEA, P = 0.02) but not associated with that of carbohydrate antigen 19-9 (P = 0.38). CRM1 levels were correlated with more advanced tumor stages (P = 0.01), positive Her2 status (P = 0.01), and distant metastasis (P = 0.02). Univariate analysis showed that CEA (P = 0.0076), TNM stage (P = 0.0001), metastasis (P = 0.027), and CRM1 expression (P = 0.0019) were significant risk factors affecting overall survival of GC patients. The multivariate analysis indicated that the CRM1 was an independent indicator for GC survival (P = 0.0048). The current results indicated that CRM1 expressed in a subpopulation of GC with aggressive behavior and could serve as a prognosis marker for poor outcome.

MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy.

Background: The mixed lineage kinase domain-like protein has recently been identified as a key downstream component of tumor necrosis factor-induced necroptosis, which is an important pathway of cancer cell death. The goal of the current study is to explore the expression of mixed lineage kinase domain-like protein in colon cancer tissues and evaluate the prognostic value in patients with colon cancer. Methods: We collected normal and cancer colon tissues from 135 patients diagnosed with colon cancer after radical operation during July 2007 to April 2009 at The Affiliated Hospital of Qingdao University. Immunohistochemistry analysis was scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival and overall survival for all patients and 2 subsets of patients. The relationship between mixed lineage kinase domain-like protein expression and prognosis parameter (recurrence-free survival, overall survival) was analyzed by univariate and multivariate Cox regression analyses. Results: The median age of all patients was 67 years and 56.3% were male. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (78.6 vs 81.2 months; P ¼ .011) in all patients. In the subset of 79 patients who received adjuvant chemotherapy, low expression of mixed lineage kinase domain-like protein was associated with decreased recurrence-free survival (60.4 vs 72.8 months; P ¼ .032) and decreased overall survival (66.3 vs 72.9 months; P ¼ .005). Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (74.9 vs 79.8 months; P ¼ .006) and recurrence-free survival (69.6 vs 78.8 months; P ¼ .005) among patients with Tumor Node Metastasis (TNM) stage II colon cancer. Conclusions: Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. It is associated with decreased recurrencefree survival and overall survival in the subset of patients who receive adjuvant chemotherapy and patients who were TNM stage II. Mixed lineage kinase domain-like protein may provide important prognostic information in patients with colon cancer.

Docetaxel is commonly used as an effective chemotherapeutic drug for gastric cancer patients recently. With the increasing emergence of docetaxel resistance nowadays, identification of suitable biomarkers for predicting chemosensitivity to docetaxel may be a key role for improving therapeutic effects for gastric cancer patients. In this study, we investigated the correlation between the expression of transcription factor forkhead box protein M1 (FOXM1) and chemotherapy response to docetaxel in gastric cancer, the possible mechanism for which was further explored. As a result, FOXM1 overexpression was shown to mediate resistance to docetaxel in gastric cancers. It altered microtubule dynamics to protect tumour cells from docetaxel-induced apoptosis. Mechanistic investigations revealed that tubulin-destabilizing protein Stathmin, which mediated docetaxel resistance in FOXM1-silenced gastric cancer cells, is a direct down-stream target of FOXM1, whereas another microtubule dynamics protein mitotic centromere–associated kinesin (MCAK), shown to be related to docetaxel resistance in gastric cancer cells, is not associated with FOXM1 expression significantly. These results were further provided by immunohistochemical analysis, indicating that FOXM1 and Stathmin expression levels were correlated in 103 post-operational gastric cancer specimens. Moreover, when we attenuated FOXM1 expression with FOXM1 inhibitor thiostrepton, docetaxel resistance in gastric cancers was found to be reversed, simultaneously with the down-regulation of FOXM1 and Stathmin. Therefore, FOXM1 can be a useful marker for predicting and monitoring docetaxel response. Through the inhibition of FOXM1, docetaxel resistance can be reversed, and thus FOXM1 could be a new therapeutic target in docetaxel-resistant gastric cancer.

Gastric cancer is one of the most common malignancy in the world. microRNAs (miRNAs) are naturally occurring noncoding RNA that control gene expression by targeting messenger RNA (mRNA) for post-transcriptional repression or cleavage. This study focused on a specific miRNA, miR-21, which was overexpressed in gastric cancer and examined the effects of miR-21 inhibitor on biological functions of gastric cancer cells and its possible mechanism. Gastric cancer cells MKN74 were treated with miR-21 inhibitor, negative control, and blank control. Cell proliferation, colony formation, migration, and invasion were assessed. Real-time PCR and western blot were applied to examine the expression of phosphatase and tens in homolog deleted on chromosome ten (PTEN)/PI3K/mTOR pathway molecules. miR-21 inhibitor markedly suppressed proliferation, migration, invasion, and colony formation of gastric cancer cells. Anti-miR-21 treatment also reduced the expression ratio of B cell lymphoma 2 (Bcl-2)/Bax. Furthermore, miR-21 inhibition was associated with increased expression of PTEN, which in turn decreased the ratios of S235/236, S240/244, and p-AK/AKT in gastric cancer cells. Inhibiting miR-21 modulates biological functions of gastric cancer cells via PTEN/PI3K/mTOR pathway and miR-21 inhibitor may provide a novel therapeutic strategy for gastric cancer.