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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.

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.

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.

Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression. The aim of the study is to investigate the functional roles of miR-138-5p in breast cancer (BC) cells and explore the underlying mechanisms by identifying its target gene. Our results first showed that miR-138-5p expression was remarkably decreased in BC tissues and cells using quantitative real-time PCR analysis. Forced expression of miR-138-5p significantly suppressed cell migration and invasion ability of BC using transwell assay. Moreover, miR-138-5p overexpression suppressed cell epithelial–mesenchymal transition (EMT) phenomenon of BC by upregulating E-cadherin expression, but downregulating N-cadherin and Vimentin expression. More importantly, rhomboid domain-containing protein 1 (RHBDD1) was predicted as the direct target of miR-138-5p by TargetScan and miRanda, which was subsequently confirmed by luciferase reporter assay in BC cells. RHBDD1 was up-regulated in BC tissues and negatively correlated with miR-138-5p expression. Furthermore, forced expression of miR-138-5p could down-regulate the expression of RHBDD1, but overexpression of RHBDD1 reversed the suppressive effects of miR-138-5p in BC cell migration, invasion and EMT. Our findings revealed the tumor-suppressive role of miR-138-5p in regulating BC migration by targeting RHBDD1, suggesting that miR-138-5p negatively regulating EMT might be a therapeutic target in BC.

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 hematoxylin‑eosin staining. mRNA expression levels were determined using reverse transcription‑quantitative 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 SHH‑smoothened receptor inhibitor) interfered with SHH‑mediated 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.

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.

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.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.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 aged70 years (27.5%;19/69; p0.05), 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 (p0.05). 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, p0.001), curative effect of platinum-based regimen (r=0.403, p0.001), progression-free survival/PFS (r=-0.486, p0.001) and overall survival/OS (r=-0.552, p0.001). Furthermore, the OPN expression was an independent predictor of PFS and OS for patients with advanced NSCLC after receiving platinum-based first-line chemotherapy (p0.001).OPN expression is an independent predictor of response to platinum-based first-line chemotherapy and of the prognosis of patients with advanced NSCLC.

Vasohibin-1 (VASH1) is a newly discovered angiogenesis inhibitor that is specifically expressed in human vascular endothelial cells in response to vascular endothelial growth factor and fibroblast growth factor-2. This study aimed to evaluate the expression of VASH1 in non-small cell lung cancer (NSCLC) and correlates its expression with the clinicopathological parameters and prognosis of the disease. Immunohistochemical analysis was used to determine the expression of VASH1 in NSCLC tissue and adjacent normal tissue from 84 patients. The relationship between VASH1 expression and clinicopathological indicators was examined with the chi-squared test. Moreover, the survival rate was calculated with the Kaplan–Meier survivor curve. Finally, the correlation between the indicators and patient survival was estimated with Cox analysis. VASH1 was high expressed in 63.1 % of NSCLC tissues versus 21.4 % of adjacent tissues (P < 0.01). High VASH1 expression in NSCLC tissue was correlated with clinicopathological features including lymph node status (P = 0.024) and TNM stage (P = 0.036). The Kaplan–Meier curve indicated that the patients with high VASH1 expression had significantly shorter survival than those with low VASH1 expression. In the multivariate Cox regression model, high VASH1 expression was identified as an independent prognostic factor for patients with NSCLC. High VASH1 expression is predictive of poor prognosis of NSCLC, implying that VASH1 may be a promising new target for targeted therapies for NSCLC.