SUMO4 small interfering RNA attenuates invasion and migration via the JAK2/STAT3 pathway in non-small cell lung cancer cells.

Small ubiquitin-like modifier 4 (SUMO4) is the latest member of the sumoylation family, which enhances the stability of protein, regulates the distribution and localization of the protein, and affects the transcription activity of the protein. However, the role of SUMO4 in non-small cell lung cancer (NSCLC) has not yet been reported. The present study first demonstrated that SUMO4 was upregulated in a number of tissues from patients with NSCLC. Immunohistochemistry was performed to demonstrate the expression level of SUMO4 in lung cancer tumor tissues. Following the transfection, The EMT status and signaling pathway activation regulated by SUMO4-siRNA was assessed by western blotting. The Transwell and wound healing assays were performed to investigate the regulatory effect of SUMO4-siRNA on cell migration and invasion. Cell Counting Kit-8 assay was performed to investigate whether SUMO4-siRNA affected the chemosensitivity of the NSCLC cells to cisplatin. Statistical analysis of immunohistochemical results from the tissues showed that the overexpression of SUMO4 was significantly associated with sex, tumor type, history of smoking, T stage and poor prognosis. It was also identified that SUMO4 small interfering RNA attenuated invasion and migration in NSCLC cell lines, as well chemosensitivity to cisplatin via the inhibition of the JAK2/STAT3 pathway. In conclusion, SUMO4 may play an important role in the poor prognosis of patients with NSCLC. The present study indicates that SUMO4 may be a potential therapeutic target for NSCLC.

The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/ß-catentin signaling.

BACKGROUND: Non-small-cell lung cancer (NSCLC) remains a highly prevalent and deadly form of cancer, with efforts to better understand the molecular basis of the progression of this disease being essential to its effective treatment. Several recent studies have highlighted the ability of RNA-binding proteins (RBPs) to regulate a wide range of cellular processes in both healthy and pathogenic contexts. Among these RBPs, RNA binding motif protein 47 (RBM47) has recently been identified as a tumor suppressor in both breast and colon cancers, whereas its role in NSCLC is poorly understood. METHODS: RBM47 expression in NSCLC samples was evaluated by RT-PCR, western blotting and immunohistochemistry analysis. Molecular and cellular techniques including lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of RBM47. RESULTS: This study sought to analyze the expression and role of RBM47 in NSCLC. In the present study, we observed reduced levels of RBM47 expression in NSCLC, with these reductions corresponding to a poorer prognosis and more advanced disease including a higher TNM stage (p = 0.022), a higher likelihood of tumor thrombus (p = 0.001), and pleural invasion (p = 0.033). Through functional analyses in vitro and in vivo, we further demonstrated that these RBP was able to disrupt the proliferation, migration, and invasion of NSCLC cells. At a molecular level, we determined that RBM47 was able to bind the AXIN1 mRNA, stabilizing it and thereby enhancing the consequent suppression of Wnt/ß-catentin signaling. CONCLUSION: Together our findings reveal that RBM47 targets AXIN1 in order to disrupt Wnt/ß-catenin signaling in NSCLC and thereby disrupting tumor progression. These results thus offer new insights into the molecular biology of NSCLC, and suggest that RBM47 may also have value as a prognostic biomarker and/or therapeutic target in NSCLC patients.

Expression and clinical significance of p75NTR in esophageal squamous cell carcinoma.

Objectives: To analyze the expression and clinical significance of p75NTR in esophageal squamous cell carcinoma. Methods: Sixty patients with esophageal squamous cell carcinoma who underwent surgical resection in our hospital between January 2017 and January 2018 were selected as the study subjects. The content of the study was in accordance with medical ethics and approved by the medical ethics committee, and patients understood and signed an informed consent form. The clinical data of all patients were analyzed retrospectively. The positive rate of p75NTR in lymph node metastasis-positive patients, lymph node metastasis-negative patients and patients with invasion of the muscle layer was detected and statistically analyzed. Results: Lymph node metastasis-positive patients had a p75NTR-positive rate of 100.00% (30/30), which was significantly higher than that of lymph node metastasis-negative patients (20.00% (6/30)) (P < 0.05) The p75NTR-positive rate in patients with infiltration of the muscular layer was 73.33% (20/30), which was significantly higher than that of patients with infiltration of the whole layer (43.33% (13/30) (P < 0.05). Conclusions: The high expression of p75NTR in esophageal squamous cell carcinoma tissue can indicate the invasion depth of the cancerous tissue and lymph node metastasis, and the clinical introduction of the p75NTR index can be the basis for an effective prognosis prediction in patients with esophageal squamous cell carcinoma.

Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy.

BACKGROUND: Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms - FAS -670 A>G, FAS ligand -844 T>C, survivin -31 G>C, and survivin 9386 C>T - with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy. MATERIALS AND METHODS: Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique. RESULTS: Patients with the CC genotype of FAS -670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS -670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively). CONCLUSION: The functional FAS -670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up.

The p53 protein is involved in many biological functions in cancer, such as cell cycle arrest, DNA repair, apoptosis, senescence, DNA metabolism, angiogenesis, and cellular differentiation. However, the association between p53 expression and clinicopathological findings or prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. We designed a large-scale study of 830 operable ESCC patients with a long follow-up to investigate the relationship between p53 expression and the clinicopathological characteristics and prognosis of patients. Immunohistochemistry was used to detect p53 protein expression. When the patients were divided into two groups, a positive expression group and a negative expression group, p53-positive expression positively correlated with a poorer differentiation level (P = 0.044). The overexpression of p53 was associated with a more advanced clinical stage (P = 0.015). A total of 775 patients were available for survival analysis. The median OS of 160 patients who had p53-positive expression and 486 patients who had p53-negative expression were 58.8 and 46.3 months, respectively (P = 0.021); the median PFS of the two groups were 39.6 and 27.5 months, respectively (P = 0.015). Lymph node metastasis, gender, differentiation, depth of invasion, and p53 protein expression were proven to have an influence on both OS and PFS in a univariate analysis. In the multivariate analysis, p53-positive expression maintained its independent prognostic impact on OS (P = 0.048) and PFS (P = 0.039), as did lymph node metastasis, differentiation, and depth of invasion. We identified that p53 protein-positive expression can serve as an independent, unfavorable prognosis biomarker in ESCC.