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Aim: CC chemokine receptor 9 (CCR9) interacts with its exclusive ligand CCL25, resulting in promoting tumor progression and metastasis. However, the effect and mechanisms of CCR9 on lung adenocarcinoma distant metastasis remain largely unknown. To preliminary clarify the underlying mechanisms, we investigate the correlation between CCR9 and ALDH1A1+cancer stem cells (CSCs), as well as the effect of CCR9 on the migration and invasion of CSCs. Methods: Immunohistochemistry was performed to detect the expression of CCR9 in lung adenocarcinoma tissues. The correlations of CCR9 with distant metastasis and overall survival were investigated. Serial paraffin-embedded tissue blocks were used to detect ALDH1A1+CSCs expression. The correlations between CCR9 expression and ALDH1A1+CSCs were evaluated. We further studied the effect of CCR9/CCL25 on the migration and invasion of CSCs using transwell assays. Results: There were positive correlations between CCR9 expression and distant metastasis, as well as poor overall survival. Patients with high CCR9 expression were more likely to develop distant metastasis and demonstrated poorer overall survival than patients with low CCR9 expression. In addition, there was positive correlation between the expression of CCR9 and ALDH1A1 in the same tumor microenvironment. ALDHhigh CSCs demonstrated enhanced expression of CCR9 than ALDHlow cells. Further transwell assays demonstrated that the numbers of CSCs migrated or invaded in response to CCL25 were more than that without CCL25 stimulation. Additional application of anti-CCR9 antibody reversed the CCL25-induced migration and invasion of CSCs. Conclusions: In summary, our study demonstrated that CCR9/CCL25 promoted the migration and invasion of CSCs, which might contribute to distant metastasis and poor overall survival. Our findings provided evidence that CCR9/CCL25 could be used as novel therapeutic targets for lung adenocarcinoma.

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL.

Lung squamous cell carcinoma (LUSCC), as the major type of lung cancer, has high morbidity and mortality rates. The prognostic markers for LUSCC are much fewer than lung adenocarcinoma. Besides, protein biomarkers have advantages of economy, accuracy and stability. The aim of this study was to construct a protein prognostic model for LUSCC. The protein expression data of LUSCC were downloaded from The Cancer Protein Atlas (TCPA) database. Clinical data of LUSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 237 proteins were identified from 325 cases of LUSCC patients based on the TCPA and TCGA database. According to Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, a prognostic prediction model was established which was consisted of 6 proteins (CHK1_pS345, CHK2, IRS1, PAXILLIN, BRCA2 and BRAF_pS445). After calculating the risk values of each patient according to the coefficient of each protein in the risk model, the LUSCC patients were divided into high risk group and low risk group. The survival analysis demonstrated that there was significant difference between these two groups (p= 4.877e-05). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was 0.699, which suggesting that the prognostic risk model could effectively predict the survival of LUSCC patients. Univariate and multivariate analysis indicated that this prognostic model could be used as independent prognosis factors for LUSCC patients. Proteins co-expression analysis showed that there were 21 proteins co-expressed with the proteins in the risk model. In conclusion, our study constructed a protein prognostic model, which could effectively predict the prognosis of LUSCC patients.

Background:The expression and biological roles of a novel lncRNA HOXC-AS3 in cervical squamous cell carcinoma (CESC) are largely unknown.Methods:LncRNA HOXC-AS3 was identified from The Cancer Genome Atlas (TCGA) database. Real time quantitative PCR (qRT-PCR) was used to evaluate the expression of HOXC-AS3 in 68 pairs of CESC tumor tissues and adjacent normal tissues. Kaplan-Meier survival analysis was used to assess the significance of HOXC-AS3 in predicting overall survival (OS). Correlations between HOXC-AS3 expression and clinicopathological parameters were assessed using Chi-square test. The biological functions of HOXC-AS3 in CESC were investigated using loss-of and gain-of function assays, which including cell proliferation, migration and invasion. Furthermore, the underlying mechanism was revealed using bioinformatics prediction, qRT-PCR and western blot.Results:HOXC-AS3 expression was significantly up-regulated in CESC tumor tissues. Up-regulated HOXC-AS3 expression was correlated with advanced stage and poor OS. Over-expression of HOXC-AS3 promoted tumor cell proliferation, migration and invasion. Conversely, HOXC-AS3 knockdown significantly inhibited these effects. Subcellular fractionation analysis revealed that HOXC-AS3 was mainly localized in cell nuclei. Further mechanistic analyses demonstrated that HOXC-AS3 down-regulated the expression of FBXL17. The promotive effects of HOXC-AS3 on cell proliferation, migration and invasion could be repressed by FBXL17. Moreover, HOXC-AS3 activated the EMT process to promote the progression of CESC. Conclusion:In conclusion, our study indicated that HOXC-AS3 acted as an oncogenic lncRNA in CESC through downregulating FBXL17 expression and activating EMT process.

Aim The human ubiquitination factor E4B (UBE4B) gene is frequently amplified in some solid cancers. However, the role of UBE4B in nasopharyngeal carcinoma (NPC) has not yet been investigated. Methods Firstly, we analyzed the expression of UBE4B in NPC samples using real-time quantitative PCR and Western blot analysis. After knocking down UBE4B using small interfering RNA technology, the functions of UBE4B on cell proliferation, apoptosis, and cell cycle, as well as underlying mechanism, were investigated. Results Compared with matched adjacent non-tumor tissues, both protein and mRNA levels of UBE4B were much higher in most NPC cancerous specimens. Deficiency of UBE4B could significantly inhibit tumor cell growth and induce cell apoptosis. Knocking down UBE4B could promote the expression of cleaved caspase3 and p53, and inhibition of caspase3 could prevent cell apoptosis induced by the deficiency of UBE4B. Conclusion These results indicate that expression of UBE4B was higher in most NPC tissues compared to adjacent non-tumoral tissues, and that knockdown of UBE4B inhibited the cell growth and induced apoptosis in NPC cells. This process was regulated by the activation of caspase3 and p53. Thus, UBE4B gene might act as a potential molecular target to develop novel strategy for NPC patients.

Background MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. Methods Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. Results We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. Conclusions These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway.

Highlights • NSE expression was positively correlated with distant metastasis of SCLC. • NSE promotes migration, invasion and EMT process of SCLC cells. • Wnt/β-catenin signaling pathway is activated in the NSE-overexpressing SCLC cells. • NSE interacts with β-catenin and inhibits the degradation of β-catenin., Neuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. In this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration and invasion of SCLC cells. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and distant metastasis of SCLC cells in vivo. In summary, our results revealed that NSE could promote the EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting cell migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

BackgroundNeuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. MethodsWe conducted an investigation in SCLC patients and then analyzed the association between NSE concentration and the distant metastasis. The migration and invasion were analyzed using Wound-healing and Transwell assays. The proteins and mRNA levels were measured by western blot and qRT-PCR. Furthermore, we conducted Gene Set Enrichment Analysis (GSEA) to explore potential signaling pathways. The interaction between NSE and β-catenin was verified through CO-IP experiments. In addition, animal experiments were performed in tumor metastasis models of nude mice.ResultIn this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration, invasion and metastasis of SCLC cells, while knocking down NSE inhibited these effects. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells, while knocking down NSE inhibited this effect. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and tumor distant metastasis of SCLC cells by activating Wnt/β-catenin pathway in vivo.ConclusionOur results revealed that NSE could promote EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

The aim of the present study was to investigate the significance of aberrant expression of mammalian target of rapamycin (mTOR) and the activated form of mTOR kinase, phosphorylated mTOR (pmTOR), in human stage IIIB colon cancer. The expression of mTOR and pmTOR was detected by immunohistochemistry in the tumor tissue of stage IIIB colon cancer patients. The association between the expression of mTOR, pmTOR and clinicopathological parameters of patients was analyzed. The positive expression of mTOR and pmTOR was observed to be higher in 75.5% (80/106) and 76.4% (81/106) of the 106 colon cancer specimens, compared with the adjacent normal tissues. The high level of pmTOR expression was found to be significantly higher in the invasive tumor front cells and resulted in a higher risk of mortality. The results suggested that mTOR and pmTOR may be promising clinical markers and present novel molecular targets for designing novel therapeutic strategies to treat this malignancy.

The objectives of this study were to examine the expression levels of Homeobox A10 (HoxA10) in prostate cancer cells and to study the molecular mechanism of HoxA10-mediated regulation of prostate cancer cell growth and development. We investigated the effect of HoxA10 on cell proliferation by stably overexpressing or silencing HoxA10 in prostate cancer PC-3 cell line using lentiviral vectors. Quantitative real-time PCR and western blotting analysis were used to compare the expressions of HoxA10 in prostate cancer cell lines and normal prostate epithelium. Cancer cell proliferation was examined by MTT assay and colony formation assay. The levels of HoxA10 expression were significantly increased in prostate cancer cell lines and tissues compared to those in normal prostate epithelium. Overexpression of HoxA10 in PC-3 cells induced significant cancer cell proliferation, whereas silencing of HoxA10 expression by RNAi resulted in decreased proliferation rates. HoxA10 was highly expressed in prostate cancer cells and tissues, suggesting its functional involvement in cancer cell proliferation. We successfully overexpressed or silenced HoxA10 in prostate cancer PC-3 cell line and discovered that the levels of HoxA10 directly correlate with cancer cell proliferation. These findings contribute to a better understanding of the regulatory mechanism of HoxA10 in prostate cancer.

An IP camera based on TI's DaVinci DSP-TMS320DM6437 is developed in this paper. An intelligent video surveillance system is established using the designed IP camera. The real-time capture of the video is implemented in the system as well as the compression coding of the video using H.264 and the transmission of the encoded video through network. In the section of network communication, the performance of DSP processor in three scenes is tested, which is convenient for developers to optimize.