The expression of the SRY-Box Transcription Factor 15 (Sox15) is reduced by DNA methylation, and its progression is suppressed within numerous tumors. However, its effect on hepatocellular carcinoma (HCC) remains unknown. In the present work, the clinical importance and function of Sox15, as well as the underlying molecular mechanism, were explored within HCC. The expression of Sox15 is reduced and positively correlated with prognosis in HCC as analyzed by GEPIA (Gene Expression Profiling Interactive Analysis) and OncoLnc. Meanwhile, the hypermethylated Sox15 promoter CpG-site predicted a dismal HCC prognosis. Besides, ectopic Sox15 expression within the HCC cells (LM3, HUH7, SK-hep-1) remarkably inhibited in vitro cell growth and inhibited xenograft tumorigenesis in the nude mice. Moreover, Sox15 inactivated the Wnt pathway under both in vivo and in vitro conditions. To summarize, Sox15 played a tumor suppressor role within the HCC via the inactivated Wnt pathway. Sox15 and CpG-site methylation of its promoter are the factors that independently predict the prognosis of HCC.

Keratin 8 (KRT8) is the major component of the intermediate filament cytoskeleton and aberrant expression in multiple tumors. However, the role of KRT8 in lung adenocarcinoma (LUAD) remains unclear. In the present study, KRT8 expression was found to be upregulated along with prognosis and metastasis in LUAD. Kaplan–Meier analysis presented that the 5-year OS and DSS rates were significantly better among patients with low KRT8 expression compared to those with high expression. Correlation analysis showed that KRT8 expression was significantly associated with gender (P = 0.027), advanced T stage (P = 0.001), advanced N stage (P = 0.048), and advanced pathologic stage (P = 0.025). Univariate Cox analysis demonstrated that KRT8 was a predictor of OS [hazard ratio (HR) = 1.526; 95% confidence interval (CI) 1.141–2.040; P = 0.004] and DSS (HR = 1.625; 95% CI 1.123–2.353; P = 0.010) in the TCGA database. Importantly, downregulation of KRT8 obviously suppressed cell proliferation, cell migration, invasion, and EMT as well as induced cell apoptosis. KRT8 knockdown significantly inhibited NF-κB signaling, suggesting a potential mechanism. Overall, our results indicated that KRT8 could regulate lung carcinogenesis and may serve as a potential target for antineoplastic therapies.

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC.

Background: To investigate the roles of gastrin-releasing peptide (ProGRP) in the diagnosis of small cell lung cancer (SCLC). Methods: We retrospectively analyzed data from 11,206 patients with clinical suspicion of lung cancer from January 1, 2015 to May 31, 2018. ProGRP and neuron-specific enolase (NSE) were detected in peripheral blood, and receiver operating characteristic curve (ROC) was used for analysis. Results: ROC indicated that the cutoff values of ProGRP and NSE were 66 ng/L and 18 mu g/L respectively, and the diagnosis efficacy of ProGRP was greater than that of NSE (sensitivity: 86.5% vs. 78.8%; specificity: 96.5% vs. 86.3%, respectively) in the diagnosis of SCLC. Moreover, the median level of ProGRP in SCLC increased with the accompanying stages (P<0.001). Further analysis showed that diagnostic efficacy can be improved by using different cutoff values in different stages, but not stage I and II. The cut-off values of ProGRP in the diagnosis of SCLC in stage I-II, III and IV were 56, 71 and 99 ng/L respectively. In addition, the sensitivity (96.6% vs. 95.8% and 98.3% vs. 94.8%) and concordance rate (chi(2) = 1,526.9 and 988.7, both P<0.001) of detecting SCLC was improved by using different cutoff values compared with the only criteria of ProGRP being >= 66 ng/L in stage III and IV, but not stage I-II Additionally, in stage III and IV, the concordance rates of ProGRP >= 71 ng/L and ProGRP >= 99 ng/L were also higher than ProGRP >= 300 ng/L (both P<0.001), which was conventionally indicated for SCLC. Conclusions: ProGRP has significantly higher sensitivity and specificity than NSE in the diagnosis of SCLC. Furthermore, special thresholds for every stage may be more reasonable for the diagnosis of SCLC.

Colon cancer is a common type of cancer worldwide and accounts for a significant number of cancer‑related deaths. Although surgical techniques and treatment strategies for colon cancer have advanced over the past two decades, the prognosis has not improved considerably. Resveratrol, a natural stilbene compound, possesses antioxidant, cardioprotective and anticancer properties. However, the role of resveratrol in colon cancer has not been fully elucidated. The present study demonstrated that resveratrol inhibited cell proliferation and colony growth in DLD1 and HCT15 colon cancer cells, but did not affect normal colon epithelial cells. The resveratrol‑mediated inhibition of cell proliferation correlated with an induction of apoptosis and with G1 phase cell cycle arrest in colon cancer cells. Additionally, resveratrol treatment decreased the protein expression levels of cyclin D1, cyclin E2 and BCL2 apoptosis regulator, while it increased BCL2 associated X and tumor protein p53, all of which are involved in the regulation of cell cycle and apoptosis. Notably, the results obtained from in silico computational screening identified AKT serine/threonine kinase 1 (AKT1) and AKT2 as novel targets of resveratrol. Computational docking suggested that there are three or four possible hydrogen bonds in the active pocket of AKT1 and AKT2 that contribute to the mode of action of resveratrol. The present study confirmed that resveratrol bound to AKT1 and AKT2 with a pull‑down assay. Furthermore, knockdown of AKT1 and AKT2 inhibited cell proliferation and colony growth, by attenuating cell cycle progression and increasing apoptosis in colon cancer cells, effects that were similar to those caused by resveratrol treatment. Taken together, the present results suggest that the targeting effects of resveratrol to AKT1 and AKT2 may be a potent strategy for chemoprevention or therapy for colon cancer.

BACKGROUND:The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer.METHODS:For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate.RESULTS:There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups.CONCLUSIONS:These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.