CircVDAC3 sequesters microRNA-592 and elevates EIF4E3 expression to inhibit the progression of gastric cancer.

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.

The influence of pharmaceutical care in patients with advanced non-small-cell lung cancer receiving combination cytotoxic chemotherapy and PD-1/PD-L1 inhibitors.

Background: Immune checkpoint inhibitors combined chemotherapy (ICIC) are widely used for various types of lung cancer in the past decade. However, ICIC related adverse events (AEs) are more serious than immune-related adverse events (irAE) or cytotoxic chemotherapy alone. Objective: This prospective interventional study aimed to evaluate the impact of the pharmaceutical care program in reducing adverse events and analyze pharmacy interventions in patients with NSCLC who receive ICIC therapies. Method: NSCLC patients were enrolled in this study, the pharmaceutical care program was introduced after patients received the second cycle ICIC therapies, and were followed by the pharmacist for 6 months after hospital discharge. The percentages of adverse events between patients in and after the first two cycles were analyzed and compared. Results: After the first two treatment cycles, the clinical pharmacist proposed 67 interventions in 30 patients. The most frequent types of intervention were drug discontinuation (40.3%, 27/67) followed by drug modification (14.9%, 10/67). There were significant decreases in AEs after the second cycle with respect to nausea (≥grade-2, 14% vs. 28.3%, p = 0.039), constipation (≥grade-2, 8.8% vs. 21.7%, p = 0.039), diarrhea (≥grade-2, 6% vs. 16.7%, p = 0.031), and myelosuppression (≥grade-2, 15.8% vs. 30.0%, p = 0.022). Conclusion: Provision of pharmaceutical care for NSCLC patients receiving ICIC therapies can optimize drug therapy and reduce adverse events.

MYC/MAX-Activated LINC00958 Promotes Lung Adenocarcinoma by Oncogenic Transcriptional Reprogramming Through HOXA1 Activation.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The role of the long non-coding RNA (lncRNA) LINC00958, which regulates the malignant behavior of multiple tumors, in LUAD has not been elucidated. METHODS: Tissue microarray, FISH, and qRT-PCR were used to detect the expression of LINC00958. Plasmid and viral infections were used to manipulate gene expression. The role of LINC00958 in LUAD was studied by cell proliferation analysis, cell apoptosis analysis, cell migration and invasion analysis, and subcutaneous inoculation of animal models. At the same time, RNA-Seq, RNA pull-down, ChIRP, ChIP, and luciferase reporter gene assays were performed to clarify the mechanism. RESULTS: The expression of LINC00958 in LUAD tissues was significantly upregulated when compared with that in adjacent tissues and could independently predict poor survival of patients with LUAD. LINC00958 knockdown significantly inhibited the growth and metastasis of lung cancer cells in vitro and in vivo. LINC00958 localized to the nucleus, regulated oncogenes and metabolism-related and immune response-related genes, and interacted with histones. The targets of LINC00958 were TRPV3, STAP2, and EDN2 promoters with motifs of HOXA1, NANOG, FOSL2, JUN, and ATF4. Moreover, HOXA1 overexpression mitigated the LINC00958 knockdown-induced oncogenic phenotype. MYC/MAX motif, which was detected at the cis-element of LINC00958, trans-activated the LINC00958 promoter. CONCLUSIONS: MYC/MAX-trans-activated LINC00958 promotes the malignant behavior of LUAD by recruiting HOXA1 and inducing oncogenic reprogramming.

Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study.

OBJECTIVE: To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF). METHODS: The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events. RESULTS: A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while ß-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor. CONCLUSION: Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.

ELK1 Promotes Epithelial-Mesenchymal Transition and the Progression of Lung Adenocarcinoma by Upregulating B7-H3.

In previous studies, we found that B7 homolog 3 (B7-H3) was highly expressed in lung adenocarcinoma (LUAD) and promoted epithelial-to-mesenchymal transition (EMT) of LUAD cells. However, the underlying molecular mechanism is unclear. This study is aimed at evaluating the role of Ets-like protein 1 (ELK1) as a transcriptional regulator of B7-H3 for mediating the development and progression of LUAD in vitro and in vivo. We confirmed that ELK1 is highly expressed in LUAD and is associated with poor patient prognosis. ELK1 was found to promote proliferation, invasion, migration, and EMT of LUAD cells through in vivo and in vitro experiments. In terms of mechanism, ELK1 binds to the B7-H3 promoter region and induces the upregulation of B7-H3 in LUAD. Our data suggest that ELK1 plays an important role in the development of LUAD and could be used as a prognostic marker and therapeutic target for LUAD.

Quantitative proteomics identified 3 oxidative phosphorylation genes with clinical prognostic significance in gastric cancer.

The aim of the present study was to explore the underlying mechanisms involved in gastric cancer (GC) formation using data-independent acquisition (DIA) quantitative proteomics analysis. We identified the differences in protein expression and related functions involved in biological metabolic processes in GC. Totally, 745 differentially expressed proteins (DEPs) were found in GC tissues vs. gastric normal tissues. Despite enormous complexity in the details of the underlying regulatory network, we find that clusters of proteins from the DEPs were mainly involved in 38 pathways. All of the identified DEPs involved in oxidative phosphorylation were down-regulated. Moreover, GC possesses significantly altered biological metabolic processes, such as NADH dehydrogenase complex assembly and tricarboxylic acid cycle, which is mostly consistent with that in KEGG analysis. Furthermore the higher expression of UQCRQ, NDUFB7 and UQCRC2 were positively correlated with a better prognosis, implicating these proteins may as novel candidate diagnostic and prognostic biomarkers.

The NAC transcription factor CaNAC064 is a regulator of cold stress tolerance in peppers.

NAC (NAM, ATAF1/2 and CUC2) proteins are plant-specific transcription factors (TFs) that are important in plant abiotic stress responses. In this study we isolated a NAC gene from Capsicum annuum leaves, designated as CaNAC064. We characterized the amino acid sequence of CaNAC064 and found that it contain conserved domains of the NAC family, including a highly conserved N-terminus domain and a highly variable C-terminus domain. Expression analysis showed that the 40C, 400C, salicylic acid (SA) and abscisic acid (ABA) treatments strongly induced the expression of CaNAC064 through silencing of CaNAC064 in pepper and overexpressing in Arabidopsis. CaNAC064-silenced pepper plants exhibited more serious wilting, higher MDA contents and chilling injury index, lower proline content, and more accumulation of ROS in the leaves after cold stress. The CaNAC064-overexpressing Arabidopsis plants exhibited lower MDA content, chilling injury index and relative electrolyte leakage content as compared to WT plants under cold stress. Transcriptional activation activity analysis indicated that CaNAC064 has transcriptional activation activity in the 691-1071 bp key region. We identified 45 proteins that putatively interact with CaNAC064 using the Yeast Two-Hybrid method. According to the Yeast Two-Hybrid and BIFC results, CaNAC064 interacted with low temperature-induced haplo-proteinase proteins in plant cell. These results suggested that CaNAC064 positively modulates plant cold-tolerance, laying the foundation for future investigations into the role of NACs as regulatory proteins of cold tolerance in plants.

TRPM7 deficiency suppresses cell proliferation, migration, and invasion in human colorectal cancer via regulation of epithelial-mesenchymal transition.

BACKGROUND: It has been documented that transient receptor potential melastatin 7 (TRPM7) plays a pivotal role in the development of multiple cancers. However, the role of TRPM7 in human colorectal cancer (CRC) is poorly understood. Therefore, the aim of this study was to investigate the expression and significance of TRPM7 in CRC. METHODS: In this study, TRPM7 expression was first investigated in Gene Expression Omnibus (GEO), and then validated it with the data from our medical center. CCK-8, colony survival, transwell, and flow cytometry assays were employed to evaluate the effects of TRPM7 knockdown on the CRC cell proliferation, migration, and invasion, as well as cell cycle and apoptosis. RESULTS: We observed markedly increased TRPM7 expression in CRC tissues. CRC patients with high expression of TRPM7 suggested deeper tumor infiltration, positive lymph node metastasis, distant metastasis, and advanced clinical stage. In addition, TRPM7 was also overexpressed in CRC cell lines. Downregulated TRPM7 in vitro suppressed CRC cell proliferation, migration, and invasion, as well as triggered cell cycle arrest at the G0/G1 phase, reduced the S phase, and promoted apoptosis. Importantly, decreased TRPM7 in CRC cells reversed the epithelial-mesenchymal transition (EMT) status, accompanied by downregulation of N-cadherin and upregulation of E-cadherin. CONCLUSION: Our study indicated that the expression of TRPM7 was positively correlated with tumor infiltration, lymph node metastasis, distant metastasis and clinical stage of CRC. Besides, decreased TRPM7 in vitro inhibited CRC cell proliferation, migration and invasion by modulating EMT.

Knockdown of CHPF suppresses cell progression of non-small-cell lung cancer.

Purpose: The aim of the present study was to explore the role of CHPF in non-small-cell lung cancer (NSCLC) and to develop an shRNA vector-based therapy to repress the expression of CHPF gene in NSCLC cell lines. Methods: In this study, we used immunohistochemical staining to verify the expression of CHPF in NSCLC tissue. Then, we determined the expression of CHPF gene in different NSCLC cell lines with RT-PCR and Western blotting. Specific CHPF shRNA was used to knockdown the expression of CHPF. Celigo image cytometry, cell cycle analysis, and flow cytometry assay were performed. Results: The results showed that expression level of CHPF was higher in NSCLC tissues than normal lung tissues. Further, we established that CHPF expression knockdown in NSCLC cells could substantially restrain the cell proliferation, apoptosis, and cell cycle in vitro. Conclusion: On the basis of these results, we concluded that CHPF expression has an important role in the progression of human NSCLC cells. Therefore, its interference could possibly be used as a potential therapeutic target against NSCLC.

CHPF promotes lung adenocarcinoma proliferation and anti-apoptosis via the MAPK pathway.

OBJECTIVE: Recent studies have shown that Chondroitin polymerizing factor (CHPF) is abnormally expressed in malignant tumors, however, the expression of CHPF in lung adenocarcinoma (LUAD) has not been reported. In this study, the relationship of CHPF and LUAD will be explored. METHODS: Differential genes present in LUAD were screened by bioinformatics analysis. The expression status of CHPF in LUAD tissues and cell lines were deteced by Western blotting or Real-time Quantitative Polymerase Chain Reaction Detecting System (qPCR), and the relationship between CHPF and prognosis of LUAD patients was analyzed. CHPF was effectively silenced in LUAD cell lines by lentivirus- mediated methods. The effect of CHPF on proliferation, cell cycle progression and apoptosis of cancer cells was assessed. We further determined the role of CHPF in tumor growth in vivo by using xenograft LUAD tumor models. Western blotting assay was performed to assess the expression changes of MAPK signaling pathway. RESULTS: We found that CHPF is highly expressed in LUAD tissues and cell lines. In vitro experiments, CHPF knockdown in LUAD cells can effectively inhibit proliferation and promote apoptosis of cancer cell. In vivo experiment, tumor growth was markedly inhibited by CHPF knockdown in the xenograft model of LUAD. Notably, CHPF also could promote tumor progression by regulating MAPK pathway. CONCLUSION: CHPF can promote the proliferation and antiapoptosis of LUAD cells, which is promising to become a potential target for LUAD treatment.

LDH-A promotes malignant behavior via activation of epithelial-to-mesenchymal transition in lung adenocarcinoma.

Lactate dehydrogenase A (LDH-A) is a key enzyme during glycolysis, which increases the synthesis of related proteins and has elevated activity in cancer cells. The role of LDH-A in lung adenocarcinoma (LUAD) progression was investigated in the present study. Expression levels of LDH-A were assessed in LUAD samples, and the relationship between LDH-A expression status and the prognosis of LUAD patients was confirmed. The effect of LDH-A on proliferation, invasion, migration, and colony formation of cancer cells was assessed. We further determined the role of LDH-A in tumor growth in vivo by using xenograft LUAD tumor models. The potential mechanism of LDH-A promotion in LUAD progression was explored. LDH-A showed an abnormally high expression in LUAD, which is closely associated with poor prognosis in patients with LUAD. In in vitro experiments, silencing LDH-A expression in LUAD cells could effectively inhibit proliferation, invasion, migration, and colony formation of cancer cells. In in vivo experiments, tumor growth was markedly inhibited by LDH-A silencing in a xenograft model of LUAD. Notably, LDH-A could also promote tumor progression by regulating epithelial-mesenchymal transition (EMT)-related molecules. LDH-A can promote the malignant biological behaviors of LUAD cells, and thus can be a potential target for LUAD treatment.

Knockdown of TRIM66 inhibits malignant behavior and epithelial-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: The tripartite motif 66(TRIM66) is an important member of the TRIM protein superfamily, which can participate in the expression of multiple proteins, and is closely associated with the behaviors of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the effect of TRIM66 in this process in vitro using NSCLC cell lines, and the role of TRIM66 in regulating epithelial-mesenchymal transition(EMT) in NSCLC. METHODS: Western blotting was used to detect the TRIM66 protein expression levels in NSCLC cell lines and normal lung epithelial cells BEAS-2B. We silenced its expression in A549 cells by transient siRNA transfection to ascertain the function of TRIM66 in NSCLC cells. Western blotting was used to detect the expression of EMT-related proteins. RESULTS: TRIM66 protein content was highest in NSCLC cell line A549, compared with BEAS-2B, it showed that the TRIM66-siRNA group lung cancer cell proliferation was significantly reduced after knockdown of TRIM66, and knockdown of TRIM66 also suppressed invasion, migration and clonogenic ability of A549 cells. Finally, we found that siRNA-mediated TRIM66 silencing suppressed EMT by downregulating expression of N-cadherin and vimentin and upregulating that of E-cadherin in NSCLC cells, which could effectively reduce the invasive, migratory, and proliferative capacities of lung cancer cells. CONCLUSION: Silence TRIM66 expression suppressed NSCLC cell proliferation, invasion, and migration. The siRNA-mediated TRIM66 silencing could block the occurrence of EMT. TRIM66 could be a promising novel target for future NSCLC treatments.

Knockdown of fascin-1 expression suppresses cell migration and invasion of non-small cell lung cancer by regulating the MAPK pathway.

Fascin-1 is a cytoskeletal protein and it can specifically bind to F-actin, it can be abnormally expressed in a variety of solid tumors. Fascin-1 was identified as a factor for poor prognosis in non-small cell lung cancer (NSCLC). However, the relevant molecular mechanisms are not yet fully understood. In this study, the fascin-1 knockdown cells were produced by lentivirus infection, and then cell proliferation, invasion and cell migration assay were used to investigate the role of fascin-1 in NSCLC cells. The MAPK pathway related proteins were determined by western blot. In the current study, lentivirus-mediated fascin-1 knockdown significantly decreased the proliferation of NSCLC cells. Furthermore, fascin-1 silencing partly inhibited cell invasion and migration. Inhibition of fascin-1 decreased the activity of the MAPK pathway. Therefore, targeting fascin-1 may inhibit the growth and metastasis of NSCLC cells, which is a potentially effective therapeutic strategy for treating NSCLC.

Sonic hedgehog protein regulates fibroblast growth factor 8 expression in metanephric explant culture from BALB/c mice: Possible mechanisms associated with renal morphogenesis.

The sonic hedgehog (SHH) morphogen regulates cell differentiation and controls a number of genes during renal morphogenesis. To date, the effects of SHH on fibroblast growth factors (Fgfs) in embryonic kidney development remain unclear. In the present study, explants of BALB/c mouse embryonic kidney tissues were used to investigate the role of exogenous SHH on Fgf8 and Fgf10 expression levels ex vivo. Ureteric bud branches and epithelial metanephric derivatives were used to determine the renal morphogenesis with Dolichos biflorus agglutinin or hematoxylin­eosin staining. mRNA expression levels were determined using reverse transcription­quantitative polymerase chain reaction, while the protein expression levels were examined using immunohistochemistry and western blot analysis. During the initial stages of metanephric development, low levels of SHH, Fgf8, and Fgf10 expression were observed, which were found to increase significantly during more advanced stages of metanephric development. In addition, exogenous SHH protein treatment increased the number of ureteric bud branches and enhanced the formation of nephrons. Exogenous SHH reduced the Fgf8 mRNA and protein expression levels, whereas cyclopamine (an SHH­smoothened receptor inhibitor) interfered with SHH­mediated downregulation of Fgf8 expression. By contrast, exogenous SHH protein was not found to modulate Fgf10 mRNA and protein expression levels. In conclusion, these results indicate that the modulatory effects of SHH on BALB/c mouse metanephric explant cultures may involve the regulation of Fgf8 expression but not Fgf10 expression, which provides evidence for the functional role of Fgf proteins in renal morphogenesis.

Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer.

PURPOSE: Fascin-1 promotes the formation of filopodia, lamellipodia, and microspikes of cell membrane after its cross-linking with F-actin, thereby enhancing the cell movement and metastasis and invasion of tumor cells. This study explored the fascin-1 protein's expression in non-small cell lung cancer (NSCLC) tissues and its relationship with clinical pathology and prognostic indicators. METHODS: Immunohistochemical analysis was used to determine the expression of fascin-1 in NSCLC tissues. We used quantitative real-time polymerase chain reaction and western blot analysis to further verify the results. The fascin-1 expression and statistical method for clinical pathological parameters are examined by χ (2). Kaplan-Meier method is used for survival analysis. Cox's Proportional Hazard Model was used to conduct a combined-effect analysis for each covariate. RESULTS: In 73 of the 128 cases, NSCLC cancer tissues (57.0%) were found with high expression of fascin-1, which was significantly higher than the adjacent tissues (35/128, 27.3%). The results suggested that the high expression of fascin-1 was significantly correlated with lymph node metastasis (P=0.022) and TNM stage (P=0.042). The high fascin-1 expression patients survived shorter than those NSCLC patients with low fascin-1 expression (P<0.05). Univariate analysis revealed that lymph node metastasis, TNM stage, and fascin-1 expression status were correlated with the overall survival. Similarly, lymph node metastasis, TNM stage, and fascin-1 expression status were significantly associated with the overall survival in multivariate analyses by using the Cox regression model. CONCLUSION: The fascin-1 protein may be a useful prognostic indicator and hopeful new target for NSCLC patients.

Osteopontin expression is associated with platinum-based chemotherapy response and prognosis of patients with advanced non small cell lung cancer.

PURPOSE: To examine the expression of osteopontin (OPN) in patients with advanced non-small cell lung cancer (NSCLC), and to analyze the correlation of the expression level of OPN with response to platinum-based chemotherapy and the prognosis of NSCLC patients. METHODS: This retrospective study enrolled 92 patients with advanced NSCLC. All of the patients received platinum- based regimens as first-line chemotherapy. The expression of OPN in advanced NSCLC tissue was detected by immunohistochemistry. The associations between OPN expression with response to chemotherapy and the prognosis were analyzed by SPSS 17.0 statistical software. RESULTS: The positive expression rate of OPN in advanced NSCLC tissue was 36.9% (34/92). The positive expression rate of OPN was higher in patients ≥70 years old (65.2%;15/23) vs those aged <70 years (27.5%;19/69; p<0.05), which was also higher in patients with distant metastasis (51.9%;28/54) than that in patients without metastasis 15.8% (6/38) , the difference with statistically significant (p<0.05). Pearson's correlation analysis results showed that OPN expression was significantly correlated with age (r=0.338, p=0.001) , distant metastasis (r=0.368, p<0.001), curative effect of platinum-based regimen (r=0.403, p<0.001), progression-free survival/PFS (r=-0.486, p<0.001) and overall survival/OS (r=-0.552, p<0.001). Furthermore, the OPN expression was an independent predictor of PFS and OS for patients with advanced NSCLC after receiving platinum-based first-line chemotherapy (p<0.001). CONCLUSION: OPN expression is an independent predictor of response to platinum-based first-line chemotherapy and of the prognosis of patients with advanced NSCLC.

Lack of association between the XPD Lys751Gln polymorphism and colorectal cancer risk: a meta-analysis.

BACKGROUND: The xeroderma pigmentosum complementary group D (XPD) gene has been linked to the development of colorectal cancer (CRC) through disruption of DNA repair. Several studies have suggested that the XPD polymorphism Lys751Gln is associated with an increased risk of developing CRC. However, previous results remain inconclusive. Herein, we performed a meta-analysis to evaluate the potential for this relationship. METHODS: Relevant studies were retrieved from the PubMed database. Strict selection and exclusion criteria were determined, and the odds ratio with a 95% confidence interval was used to assess the strength of associations. The fixed or random effects model was selected on the basis of heterogeneity tests among studies. Publication bias was estimated using funnel plots and Egger's regression test. RESULTS: The meta-analysis included 2,961 cases and 4,539 controls from eleven studies. The results indicated that the XPD Lys751Gln polymorphism had no association with CRC risk for all genetic models (Gln-Gln versus Lys-Lys, P=0.477; Lys-Gln versus Lys-Lys, P=0.283; Lys-Gln + Gln-Gln versus Lys-Lys, P=0.562), even when compared within subgroups based on ethnicity and source of controls. CONCLUSION: Based on the results of our meta-analysis, there is no evidence of a link between the XPD Lys751Gln polymorphism and risk of CRC.

Functional analysis of FABP3 in the milk fat synthesis signaling pathway of dairy cow mammary epithelial cells.

Milk fat is the major energy component of milk, and regulation of its production relies on transcription factors sterol regulatory element-binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor gamma (PPARγ). As one of the target genes of SREBP1 and PPARγ, fatty acid-binding protein 3(FABP3) is the main protein allowing for rapid diffusion and selective targeting of long-chain fatty acids toward specific organelles for metabolism. Whether FABP3 plays an important role in milk fat synthesis signaling pathway is largely unknown. In this study, we observed the effects of FABP3 overexpression and gene silencing in dairy cow mammary epithelial cells, as well as the effects of oleic acid, stearic acid, and palmitic acid on the expressions of FABP3 and lipid droplet formation, by using quantitative reverse transcriptase (qRT)-PCR, Western blotting, and fluorescent immunostaining techniques. FABP3 upregulated the expression of SREBP1 and PPARγ to increase lipid droplet accumulation. Oleic acid, stearic acid, and palmitic acid also increased lipid droplet accumulation by affecting expression of FABP3. These findings shed new insights for understanding the mechanism of FABP3 in regulating milk fat synthesis.

The prognostic value of osteopontin expression in non-small cell lung cancer: a meta-analysis.

To investigate the association of Osteopontin (OPN) expression in tumor tissue with clinicopathological features of non-small cell lung carcinoma (NSCLC) patients. Publications assessing the clinicopathological characteristics and prognostic significance of OPN in expression NSCLC were identified up to March 2014. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between OPN expression and these clinical parameters. A total of eleven studies met the inclusion criteria, and included 1536 cases of NSCLC tumor tissue and 340 cases of normal lung tissue. The OPN expression rate in NSCLC tissue was higher than normal tissue [Odds ratio (OR) 6.427; 95% confidence interval (CI) 4.689-8.808; P = 0.000]. Simultaneously, we also found that OPN expression was positively associated with stage (OR 0.332; 95% CI 0.250-0.440; P = 0.000), lymph node metastasis (OR 3.094; 95% CI 2.295-4.172; P = 0.000), tumor size (tumor size <3 cm vs. ≥3 cm; OR 0.484; 95% CI 0.303-0.773; P = 0.002) and pathology (OR 0.611; 95% CI 0.466-0.800; P = 0.000). It was unrelated that OPN expression in NSCLC tissue with and degree of differentiation and other clinical features (P > 0.05). Experimental findings indicate that, OPN plays a crucial role in the development of NSCLC.