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Cell division control (CDC) 42 has been involved in the regulation of diverse cancers. Macrophage recruitment plays an important role in the pathogenesis and development of tumor. However, it remains unclear whether CDC42 contributes to macrophage recruitment and lung tumorigenesisSmall interference RNA (siRNA) was used to knock down CDC42 in the Lewis lung carcinoma (LLC)1. The invasion capability of CDC42 knockdown LLC1 cells was evaluated. LLC1 cells with CDC42 targeted small hairpin RNA (shRNA) were inoculated into C57BL/6 mice to establish the tumor-bearing animal model Tumor size and metastasis related proteins were measured. In addition, the invasion of macrophages in the tumor site as well as macrophage chemokine were also determined in the model.The capacity of invasion and metastasis of LLC1 cells significantly decreased when CDC42 was knocked down. When inoculated with CDC42 knockdown LLC1 cellsOur data suggest that the inhibition of CDC42 expression in lung cancer cells can significantly prevent the pathogenesis and development of tumor in an allograft tumor model

EZH2 (enhancer of zeste homolog 2) regulates epigenetic gene silencing and functions as critical regulators in various tumor progression. Macrophages infiltration promotes cancer development via stimulating tumor cell migration and invasion. However, the effect of EZH2 on macrophages infiltration, cell invasion, and migration of lung cancer remains to be investigated. In this study, we found that knockdown of EZH2 inhibited macrophages chemotaxis and decreased chemokine ligand 5 (CCL5). Wound‐healing and transwell assays results showed that migration and invasion of lung cancer cells was inhibited by EZH2 deletion. Moreover, EZH2 overexpression increased CCL5 expression. Loss‐of functional assay indicated that the promotion ability of EZH2 on macrophages chemotaxis was inhibited by CCL5 knockdown. Mechanistically, the promotion ability of EZH2 on cell migration and invasion of lung cancer was also inhibited by CCL5 knockdown. The in vivo subcutaneous xenotransplanted tumor model also revealed that silence of EZH2 suppressed lung cancer metastasis and macrophages infiltration via regulation of CCL5. In conclusion, our findings indicated that EZH2 promoted lung cancer metastasis and macrophages infiltration via upregulation of CCL5, which might be the underlying mechanism of EZH2‐induced lung cancer cell progression., xxxx

Lung adenocarcinoma (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144-5p targeting CDCA3 to inhibit LUAD proliferation.MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis. TargetScan and miRTarBase databases were adopted to predict the target genes of miRNA, and the signaling pathways involved were analyzed by gene set enrichment analysis. The functions of LUAD cells were analyzed by CCK-8, colony formation assay, stem cell spheroidization assay, and flow cytometry. The expression levels of CDCA3, p53, and cell cycle-associated proteins were evaluated by Western blot.The expression of miRNA-144-5p was significantly down-regulated in LUAD, but overexpression of it repressed proliferation and spheroidization, and promoted apoptosis of LUAD cells. By bioinformatics prediction and dual-luciferase reporter assay, miRNA-144-5p was validated to target CDCA3, thereby regulating proliferation of LUAD cells. Besides, the results of cell experiments showed that miRNA-144-5p targeting CDCA3 affected cell proliferation and apoptosis in LUAD by regulating cell cycles, and miRNA-144-5p/CDCA3 mediated the p53 signaling pathway to affect the growth of LUAD cells.Through the study of the pathogenesis of miRNA-144-5p regulating LUAD, we can better understand the molecular mechanism underlying LUAD development.

Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The treatment of advanced NSCLC can be challenging due to drug resistance. The discovery of novel cancer-testis antigens to develop new strategies for advanced metastatic NSCLC is required. AKAP4 is an oncogene discovered in some malignant tumors, and its molecular function of AKAP4 in NSCLC is unknown. This study aimed to explore the potential function of AKAP4 in the development and progression of NSCLC. AKAP-4 was found to be significantly upregulated in both clinical NSCLC tissues and NSCLC cell lines. Cell viability and migration were suppressed, apoptosis was induced, and tube formation was inhibited by the knockdown of AKAP-4, accompanied by the downregulation of VEGF, N-cadherin, EphA2, and MMP-2, and upregulation of c-AMP, PKA, and E-cadherin.

Non-small cell lung cancer (NSCLC) has high morbidity and mortality rates worldwide, and tumor metastasis is generally associated with poor prognosis. Chemotherapy resistance aggravates the challenges associated with treating NSCLC. Therefore, identifying effective targets and developing therapies based on these findings could bring novel perspectives for patients with metastatic NSCLC. The expression levels of receptor tyrosine-protein kinase erbB-2 (ERBB2) are associated with NSCLC progression. Differential microRNA (miR) expression profiles have been identified in tumors and can be used to identify multiple malignant phenotypes. miR-133a-3p expression is dysregulated in a variety of tumors. However, to the best of our knowledge, the association between miR-133a-3p and the NSCLC pathogenesis process has not been demonstrated yet. The present study revealed a decrease in miR-133a-3p expression in both tissues and cell lines, which was detected using reverse transcription-quantitative (RT-q)PCR, and western blotting and RT-qPCR demonstrated ERBB2 levels were increased at both protein and mRNA levels. Bioinformatics analysis and dual-luciferase reporter assays demonstrated that ERBB2 was a direct target of miR-133a-3p. Furthermore, MTT, wound healing and Transwell assays revealed that overexpression of miR-133a-3p suppressed proliferation, invasion and migration of NSCLC cells, respectively, effects that were inhibited following ERBB2 overexpression. In addition, immunofluorescence assays demonstrated that overexpression of ERBB2 upregulated N-cadherin expression, while E-cadherin expression was downregulated. In conclusion, the present data demonstrated that miR-133a-3p acted as a tumor suppressor by negatively regulating ERBB2 expression. The miR-133a-3p/ERBB2 axis may be a potential target for the diagnosis and treatment of NSCLC in the future.

Altered microRNA (miR) expression serves an important role in the development and progression of lung cancer. In the present study, the effect of miR-664 on proliferation, migration and invasion of lung cancer cells was assessed. The proliferation of lung cancer cells with an overexpression of miR-664 was examined via MTT assay. The Caspase-Glo3/7 assay was used to examine the effect of miR-664 on cisplatin-induced apoptosis in lung cancer cells. The migration and invasion of lung cancer cells were assessed by Transwell migration and matrigel invasion assays. Western blot analysis was used to examine the protein expression levels. miR-664 improved the proliferation of lung cancer cells and inhibited cisplatin-induced apoptosis of A549 and A427 cells. Furthermore, altered expression of miR-664 affected migration and invasion of lung cancer cells. In addition, a miR-664 mimic decreased E-cadherin expression and increased vementin and Snail expression in lung cancer cells. Notably, the expression level of protein kinase B in A549 cells was changed following altered expression of miR-664. The results of the present study suggest that miR-664 serves an essential role in tumor development and progression in lung cancer.

To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium.A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis.Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023).rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.

Eukaryotic translation initiation factor 4E (eIF4E) was shown to be upregulated in malignant human tumors. To assess the effect of downregulation of eIF4E on the prolifera- tion and invasiveness of a human lung adenocarcinoma cell line, a short hairpin (sh)RNA targeting eIF4E was constructed and transfected into A549 human lung adenocarcinoma cells. The expression of eIF4E was determined by reverse tran- scription-quantitative polymerase chain reaction and western blotting. Cell viability was assessed using a Cell Counting kit-8, and apoptosis levels and cell cycle distribution were assessed by flow cytometry. Invasiveness was assessed using Transwell chambers. Transfection of the A549 cells with eIF4E targeting shRNA reduced the mRNA and protein expression levels of eIF4E by >70% 48 and 72 h following transfection, and eIF4E targeting shRNA-transfected cells were significantly less viable compared with the cells transfected with scrambled shRNA. The rate of apoptosis was also significantly increased, significantly more cells were in the G 0/G1 phase and fewer were in the S phase, indicating cell cycle arrest. The fraction of transfected cells migrating across Transwell inserts were also reduced. In conclusion, inhibition of eIF4E suppressed cell growth and invasion, induced apoptosis and cell cycle arrest, suggesting that eIF4E may be a potential therapeutic target in lung adenocarcinoma.