No abstract

Increasing evidence indicates that the ability of cancer cells to convey biological information to recipient cells within the tumor microenvironment (TME) is crucial for tumor progression. Microvesicles (MVs) are heterogenous vesicles formed by budding of the cellular membrane, which are secreted in larger amounts by cancer cells than normal cells. Recently, several reports have also disclosed that MVs function as important mediators of intercellular communication between cancerous and stromal cells within the TME, orchestrating complex pathophysiological processes. Chemokines are a family of small inflammatory cytokines that are able to induce chemotaxis in responsive cells. MVs which selective incorporate chemokines as their molecular cargos may play important regulatory roles in oncogenic processes including tumor proliferation, apoptosis, angiogenesis, metastasis, chemoresistance and immunomodulation, et al. Therefore, it is important to explore the association of MVs and chemokines in TME, identify the potential prognostic marker of tumor, and develop more effective treatment strategies. Here we review the relevant literature regarding the role of MVs and chemokines in TME.

Background/Aims: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that regulate gene expression and are involved in physiological and pathological processes. In this study, we evaluated the roles of circRNAs in the chemoresistance of non-small cell lung cancer (NSCLC) to taxol. Methods: High-throughput circRNA microarrays were employed to investigate the circRNA profiles of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA targets of differentially expressed circRNAs via miRNA prediction software and then constructed a circRNA/miRNA network using Cytoscape. Bioinformatics analyses were performed to annotate dysregulated circRNAs in detail. Results: We detected 2909 significantly upregulated and 8372 downregulated circRNAs in A549/Taxol cells compared with A549 cells. The circRNA/miRNA network displayed their interactions, suggesting that circRNAs exert biological effects by absorbing and sequestering miRNA molecules. Computational Gene Ontology and pathway analyses were used to determine the biological function and signaling pathways of host genes of dysregulated circRNAs and to identify potential molecular mechanisms prompting the resistance of NSCLC to taxol. Conclusion: This study focusing on circRNAs related to taxol resistance provides a basis for clarifying the development and progression of drug resistance and for identifying therapeutic targets in NSCLC.

PurposeDespite new developments in cancer therapy, chemotherapy and radiotherapy remain the cornerstone of breast cancer treatment. Therefore, finding ways to reduce the toxicity and increase sensitivity is particularly important. Tumor necrosis factor alpha (TNF-α) exerts multiple functions in cell proliferation, differentiation and apoptosis. In the present study, we investigated whether TNF-α could enhance the effect of chemotherapy and radiotherapy against breast cancer cells.MethodsCell growth was determined by MTT assay in vitro, and by using nude mouse tumor xenograft model in vivo. Cell cycle and apoptosis/necrosis were evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X staining. mRNA expression was assessed by using real-time PCR. Protein expression was tested by Western blot assay.ResultsTNF-α strengthened the cytotoxicity of docetaxel, 5-FU and cisplatin against breast cancer cells both in vitro and in vivo. TNF-α activated NF-κB pathway and dependently up-regulated expressions of CyclinD1, CyclinD2, CyclinE, CDK2, CDK4 and CDK6, the key regulators participating in G1→S phase transition. As a result, TNF-α drove cells out of quiescent G0/G1 phase, entering vulnerable proliferating phases. Treatment of TNF-α brought more DNA damage after Cs137-irradiation and strengthened G2/M and S phase cell cycle arrest induced by docetaxel and cisplatin respectively. Moreover, the up-regulation of RIP3 (a necroptosis marker) by 5-FU, and the activation of RIP3 by TNF-α, synergistically triggered necroptosis (programmed necrosis). Knockdown of RIP3 attenuated the synergetic effect of TNF-α and 5-FU.ConclusionTNF-α presented radiotherapy- and chemotherapy-sensitizing effects against breast cancer cells.

Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as a primary feature of several human cancers. However, the genome-wide expression and functional significance of lncRNAs in bladder cancer remains unclear. The aim of this study was to identify aberrantly expressed lncRNAs that may play an important role in contributing to bladder cancer pathogenesis. In this study, we described lncRNAs profiles in four pairs of human bladder cancer and matched normal bladder tissues by microarray. We finally determined 3,324 differentially expressed human lncRNAs and 2,120 differentially expressed mRNAs (≥2-fold change). A total of 110 lncRNAs were significantly differentially expressed between the tumor and the control groups (≥8-fold change). Four lncRNAs (TNXA, CTA-134P22.2, CTC-276P9.1 and KRT19P3) were selected for further confirmation of microarray results using quantitative PCR (qPCR), and a strong correlation was identified between the qPCR results and microarray data. We also observed that numerous lncRNA expression levels were significantly correlated with the expression of tens of protein coding genes by construction of the lncRNA-mRNA co-expression network. Kyoto Encyclopedia of Genes and Genomes annotation showed a significant association with p53, bladder cancer, cell cycle and propanoate metabolism pathway gene expression in the bladder cancer group compared with the normal tissue group, indicating that deregulated lncRNAs may act by regulating protein-coding genes in these pathways. We demonstrated the expression profiles of human lncRNAs in bladder cancer by microarray. We identified a collection of aberrantly expressed lncRNAs in bladder cancer compared with matched normal tissue. It is likely that these deregulated lncRNAs play a key or partial role in the development and/or progression of bladder cancer.